precision medicine - cancer progress by cello health€¦ · 01/03/2016 · precision medicine...
TRANSCRIPT
Precision Medicine
Lessons from meta-analyses of 70253 patients
Razelle Kurzrock MD Senior Deputy Director Clinical Science
Director Center for Personalized Cancer Therapy and Clinical Trials Office Chief Division of HematologyOncology
UCSD Moores Cancer Center
MeeeeAeeeeeee Ceeeeeeee 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
Maria Schwaederle PharmD
Impact of a Biomarker-Based Strategy on Oncology Drug Development
A Meta-analysis of Clinical Trials Leading to FDA Approval
Denis L Fontes Jardim MD12 Maria Schwaederle PharmD3 Caimiao Wei PhD4 J Jack Lee PhD4 David S Hong MD5 Alexander M Eggermont PhD67 Richard L Schilsky MD FACP78 John Mendelsohn MD 79 Vladimir Lazar PhD67 Razelle Kurzrock MD37 1Department of Clinical Medicine Hemocentro da Unicamp University of Campinas Sao Paulo Brazil 2Department of Clinical Oncology Hospital Sirio Libanes Sao Paulo Brazil 3Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California San Diego CA USA 4Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston TX USA 5Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program) The University of Texas MD Anderson Cancer Center Houston TX USA 6Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 7Worldwide Innovative Network For Personalized Cancer Therapy 8American Society of Clinical Oncology Alexandria VA USA 9The University of Texas MD Anderson Cancer Center Houston USA
Teeeee eeeeeee ee FDA eeeeeeee
Search bull Newly approved agents from September 1998 (trastuzumab) until June 2013 bull PubMed or ASCO meetings abstracts Excluded Pediatric cancer supportive care loco-regional treatment hormonal therapies vaccines Endpoints Response rate (RR) progression-free survival (PFS) overall survival (OS) and toxicity-related deaths
Beeeeee ee eeeeeeeeeeee eeeeeee ee eeeeeeeeee
eeeeeeeeeeee eeeeee
eRRe PFSe eee OSe
Statistical analysis meta-analysis of relative response rate ratio (RRR) and hazards ratios (HRs) for PFS and OS for personalized trials versus not (random effect model) bull RRR higher likelihood of response with a personalized compared to non-personalized strategy (RRR=382 [95CI 251-582] vs 208 [95CI 176-247] (P=003 in meta-regression)
bull HR for PFS 041 (95CI 033-051) for personalized compared to 059 (95CI 053-065) for non-personalized studies (Plt001 in meta-regression)
bull HR for OS 071 (95CI 061-083) for personalized compared to 081 (95CI 077-085) for non-personalized studies (P=007 in meta-regression)
Beeeeeee ee eeeeeeeeeeee eeeeeee ee eee eeeeee
eNe112e eRRe PFSe eee OSe Stat analysis random effect meta-analysis for RR pooled analysis for PFS and OS for personalized trials versus not (weighted multiple linear regression models) bull RR 48 for personalized strategy [95CI 42-55] vs 23 [95CI 20-27] Plt001 (also Plt001 after adjustement)
bull PFS 83 months for personalized strategy vs 55 months Plt001 (P=0002 after adjustement)
bull OS 193 months for personalized strategy compared to 135 months P=001 (P=004 after adjustement) Treatment-related mortality was 158 percent for personalized versus
144 percent for non-personalized trials which was not statistically different (P=074)
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
MeeeeAeeeeeee Ceeeeeeee 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
Maria Schwaederle PharmD
Impact of a Biomarker-Based Strategy on Oncology Drug Development
A Meta-analysis of Clinical Trials Leading to FDA Approval
Denis L Fontes Jardim MD12 Maria Schwaederle PharmD3 Caimiao Wei PhD4 J Jack Lee PhD4 David S Hong MD5 Alexander M Eggermont PhD67 Richard L Schilsky MD FACP78 John Mendelsohn MD 79 Vladimir Lazar PhD67 Razelle Kurzrock MD37 1Department of Clinical Medicine Hemocentro da Unicamp University of Campinas Sao Paulo Brazil 2Department of Clinical Oncology Hospital Sirio Libanes Sao Paulo Brazil 3Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California San Diego CA USA 4Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston TX USA 5Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program) The University of Texas MD Anderson Cancer Center Houston TX USA 6Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 7Worldwide Innovative Network For Personalized Cancer Therapy 8American Society of Clinical Oncology Alexandria VA USA 9The University of Texas MD Anderson Cancer Center Houston USA
Teeeee eeeeeee ee FDA eeeeeeee
Search bull Newly approved agents from September 1998 (trastuzumab) until June 2013 bull PubMed or ASCO meetings abstracts Excluded Pediatric cancer supportive care loco-regional treatment hormonal therapies vaccines Endpoints Response rate (RR) progression-free survival (PFS) overall survival (OS) and toxicity-related deaths
Beeeeee ee eeeeeeeeeeee eeeeeee ee eeeeeeeeee
eeeeeeeeeeee eeeeee
eRRe PFSe eee OSe
Statistical analysis meta-analysis of relative response rate ratio (RRR) and hazards ratios (HRs) for PFS and OS for personalized trials versus not (random effect model) bull RRR higher likelihood of response with a personalized compared to non-personalized strategy (RRR=382 [95CI 251-582] vs 208 [95CI 176-247] (P=003 in meta-regression)
bull HR for PFS 041 (95CI 033-051) for personalized compared to 059 (95CI 053-065) for non-personalized studies (Plt001 in meta-regression)
bull HR for OS 071 (95CI 061-083) for personalized compared to 081 (95CI 077-085) for non-personalized studies (P=007 in meta-regression)
Beeeeeee ee eeeeeeeeeeee eeeeeee ee eee eeeeee
eNe112e eRRe PFSe eee OSe Stat analysis random effect meta-analysis for RR pooled analysis for PFS and OS for personalized trials versus not (weighted multiple linear regression models) bull RR 48 for personalized strategy [95CI 42-55] vs 23 [95CI 20-27] Plt001 (also Plt001 after adjustement)
bull PFS 83 months for personalized strategy vs 55 months Plt001 (P=0002 after adjustement)
bull OS 193 months for personalized strategy compared to 135 months P=001 (P=004 after adjustement) Treatment-related mortality was 158 percent for personalized versus
144 percent for non-personalized trials which was not statistically different (P=074)
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Impact of a Biomarker-Based Strategy on Oncology Drug Development
A Meta-analysis of Clinical Trials Leading to FDA Approval
Denis L Fontes Jardim MD12 Maria Schwaederle PharmD3 Caimiao Wei PhD4 J Jack Lee PhD4 David S Hong MD5 Alexander M Eggermont PhD67 Richard L Schilsky MD FACP78 John Mendelsohn MD 79 Vladimir Lazar PhD67 Razelle Kurzrock MD37 1Department of Clinical Medicine Hemocentro da Unicamp University of Campinas Sao Paulo Brazil 2Department of Clinical Oncology Hospital Sirio Libanes Sao Paulo Brazil 3Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California San Diego CA USA 4Department of Biostatistics The University of Texas MD Anderson Cancer Center Houston TX USA 5Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program) The University of Texas MD Anderson Cancer Center Houston TX USA 6Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 7Worldwide Innovative Network For Personalized Cancer Therapy 8American Society of Clinical Oncology Alexandria VA USA 9The University of Texas MD Anderson Cancer Center Houston USA
Teeeee eeeeeee ee FDA eeeeeeee
Search bull Newly approved agents from September 1998 (trastuzumab) until June 2013 bull PubMed or ASCO meetings abstracts Excluded Pediatric cancer supportive care loco-regional treatment hormonal therapies vaccines Endpoints Response rate (RR) progression-free survival (PFS) overall survival (OS) and toxicity-related deaths
Beeeeee ee eeeeeeeeeeee eeeeeee ee eeeeeeeeee
eeeeeeeeeeee eeeeee
eRRe PFSe eee OSe
Statistical analysis meta-analysis of relative response rate ratio (RRR) and hazards ratios (HRs) for PFS and OS for personalized trials versus not (random effect model) bull RRR higher likelihood of response with a personalized compared to non-personalized strategy (RRR=382 [95CI 251-582] vs 208 [95CI 176-247] (P=003 in meta-regression)
bull HR for PFS 041 (95CI 033-051) for personalized compared to 059 (95CI 053-065) for non-personalized studies (Plt001 in meta-regression)
bull HR for OS 071 (95CI 061-083) for personalized compared to 081 (95CI 077-085) for non-personalized studies (P=007 in meta-regression)
Beeeeeee ee eeeeeeeeeeee eeeeeee ee eee eeeeee
eNe112e eRRe PFSe eee OSe Stat analysis random effect meta-analysis for RR pooled analysis for PFS and OS for personalized trials versus not (weighted multiple linear regression models) bull RR 48 for personalized strategy [95CI 42-55] vs 23 [95CI 20-27] Plt001 (also Plt001 after adjustement)
bull PFS 83 months for personalized strategy vs 55 months Plt001 (P=0002 after adjustement)
bull OS 193 months for personalized strategy compared to 135 months P=001 (P=004 after adjustement) Treatment-related mortality was 158 percent for personalized versus
144 percent for non-personalized trials which was not statistically different (P=074)
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Teeeee eeeeeee ee FDA eeeeeeee
Search bull Newly approved agents from September 1998 (trastuzumab) until June 2013 bull PubMed or ASCO meetings abstracts Excluded Pediatric cancer supportive care loco-regional treatment hormonal therapies vaccines Endpoints Response rate (RR) progression-free survival (PFS) overall survival (OS) and toxicity-related deaths
Beeeeee ee eeeeeeeeeeee eeeeeee ee eeeeeeeeee
eeeeeeeeeeee eeeeee
eRRe PFSe eee OSe
Statistical analysis meta-analysis of relative response rate ratio (RRR) and hazards ratios (HRs) for PFS and OS for personalized trials versus not (random effect model) bull RRR higher likelihood of response with a personalized compared to non-personalized strategy (RRR=382 [95CI 251-582] vs 208 [95CI 176-247] (P=003 in meta-regression)
bull HR for PFS 041 (95CI 033-051) for personalized compared to 059 (95CI 053-065) for non-personalized studies (Plt001 in meta-regression)
bull HR for OS 071 (95CI 061-083) for personalized compared to 081 (95CI 077-085) for non-personalized studies (P=007 in meta-regression)
Beeeeeee ee eeeeeeeeeeee eeeeeee ee eee eeeeee
eNe112e eRRe PFSe eee OSe Stat analysis random effect meta-analysis for RR pooled analysis for PFS and OS for personalized trials versus not (weighted multiple linear regression models) bull RR 48 for personalized strategy [95CI 42-55] vs 23 [95CI 20-27] Plt001 (also Plt001 after adjustement)
bull PFS 83 months for personalized strategy vs 55 months Plt001 (P=0002 after adjustement)
bull OS 193 months for personalized strategy compared to 135 months P=001 (P=004 after adjustement) Treatment-related mortality was 158 percent for personalized versus
144 percent for non-personalized trials which was not statistically different (P=074)
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Beeeeee ee eeeeeeeeeeee eeeeeee ee eeeeeeeeee
eeeeeeeeeeee eeeeee
eRRe PFSe eee OSe
Statistical analysis meta-analysis of relative response rate ratio (RRR) and hazards ratios (HRs) for PFS and OS for personalized trials versus not (random effect model) bull RRR higher likelihood of response with a personalized compared to non-personalized strategy (RRR=382 [95CI 251-582] vs 208 [95CI 176-247] (P=003 in meta-regression)
bull HR for PFS 041 (95CI 033-051) for personalized compared to 059 (95CI 053-065) for non-personalized studies (Plt001 in meta-regression)
bull HR for OS 071 (95CI 061-083) for personalized compared to 081 (95CI 077-085) for non-personalized studies (P=007 in meta-regression)
Beeeeeee ee eeeeeeeeeeee eeeeeee ee eee eeeeee
eNe112e eRRe PFSe eee OSe Stat analysis random effect meta-analysis for RR pooled analysis for PFS and OS for personalized trials versus not (weighted multiple linear regression models) bull RR 48 for personalized strategy [95CI 42-55] vs 23 [95CI 20-27] Plt001 (also Plt001 after adjustement)
bull PFS 83 months for personalized strategy vs 55 months Plt001 (P=0002 after adjustement)
bull OS 193 months for personalized strategy compared to 135 months P=001 (P=004 after adjustement) Treatment-related mortality was 158 percent for personalized versus
144 percent for non-personalized trials which was not statistically different (P=074)
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Beeeeeee ee eeeeeeeeeeee eeeeeee ee eee eeeeee
eNe112e eRRe PFSe eee OSe Stat analysis random effect meta-analysis for RR pooled analysis for PFS and OS for personalized trials versus not (weighted multiple linear regression models) bull RR 48 for personalized strategy [95CI 42-55] vs 23 [95CI 20-27] Plt001 (also Plt001 after adjustement)
bull PFS 83 months for personalized strategy vs 55 months Plt001 (P=0002 after adjustement)
bull OS 193 months for personalized strategy compared to 135 months P=001 (P=004 after adjustement) Treatment-related mortality was 158 percent for personalized versus
144 percent for non-personalized trials which was not statistically different (P=074)
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Ieeeee ee Peeeeeeee Meeeeeee ee Deeeeee Ceeeeeee e
MeeeeAeeeeeee ee 32149 Peeeeeee ee Peeee II Ceeeeeee Teeeee
Jeeeeee ee Ceeeeeee Oeeeeeee
Maria Schwaederle PharmD1 Melissa Zhao BS1 J Jack Lee PhD2 Alexander M Eggermont MD PhD34 Richard L Schilsky MD45 John Mendelsohn MD46 Vladimir Lazar MD PhD34 Razelle Kurzrock MD14 1Center for Personalized Cancer Therapy and Division of Hematology and Oncology University of California La Jolla US 2Department of Biostatistics University of Texas MD Anderson Cancer Center Houston TX USA 3Department of Functional Genomics Institut Gustave Roussy University Paris-Sud Villejuif France 4Worldwide Innovative Network for Personalized Cancer Therapy 5American Society of Clinical Oncology Alexandria VA USA 6The University of Texas MD Anderson Cancer Center Houston USA
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
MeeeeAe eeeeee ee 32149 Peeeeeee ee Pe eee II Ceeeeeee Teeeee
bull A PubMed search was conducted (2010-2012)
bull Only single agentrsquos arms were included in the analysis
bull Exclusion criteria pediatric cancers supportive care
loco-regional treatments hormonal therapies and cellular
or vaccine therapy
bull 570 Phase II studies were included comprising 32149
patients (641 single-agent arms)
Maria Schwaederle PharmD
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
0
5
10
15
20
25
30
35
40
Personalized Not personalized
Res
pons
e ra
te (
)
Response Rate ( CI 95)
Pooled analysis
Meta-analysis
0
1
2
3
4
5
6
7
8
Personalized Not personalized
Mon
ths
Median PFS (Months CI 95)
0 2 4 6 8
10 12 14 16 18 20
Personalized Not personalized
Mon
ths
Median OS (Months CI 95)
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
POOLED Analysis Meta-analysis
ARMS type RR ()
PFS (Mos)
OS (Mos)
RR ()
PFS (Mos)
OS (Mos)
Non-personalized targeted
4 26 87 75 25 83
Cytotoxic 12 33 94 161 33 93 Personalized targeted
30 69 159 313 61 137
bull Non-personalized targeted arms led to poorer outcomes than cytotoxics arms
(All Plt00001 except P=0048 for OS meta-analysis)
Worst outcome
Best outcome
CONCLUSIONS
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
PRECISION ONCOLOGY bull Wheler JJ Parker BA Lee JJ Atkins JT Janku F Tsimberidou AM Zinner
R Subbiah V Fu S Schwab R Moulder S Valero V Schwaederle M Yelensky R Miller VA Stephens MP Meric-Bernstam F Kurzrock R Unique molecular signatures as a hallmark of patients with metastatic breast cancer Implications for current treatment paradigms Oncotarget 5(9)2349-54 2014
bull Wheler JJ Lee JJ Kurzrock R Unique Molecular Landscapes in Cancer
Implications for Individualized Curated Drug Combinations Cancer Research 74(24)7181-4 2014
bull Tsimberidou AM Iskander NG Hong DS Wheler JJ Falchook GS Fu S
Piha-Paul SA Naing A Janku F Luthra R Ye Y Wen S Berry DA Kurzrock R Personalized medicine in a Phase I clinical trials program The MD Anderson Cancer Center initiative Clinical Cancer Research 18(22)6373-83 2012
bull Kurzrock R Giles FJ Precision Oncology for Patients with Advanced
Cancer The Challenges of Malignant Snowflakes Cell Cyle 14(14)2219-21 2015 11
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
A 38-year-old man with BRAF-mutant melanoma and miliary subcutaneous metastatic deposits treated with PLX4032
(Vemurafenib)
Wagle N et al JCO 2011293085-3096
Baseline
15 weeks
23 weeks
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
NEW TRIAL DESIGNS
bull Equipoise abandoned Randomization and clinical trials
bull Kurzrock R1 Stewart DJ bull Ann Oncol 2013 Oct24(10)2471-4 doi 101093annoncmdt358
bull Fools gold lost treasures and the randomized clinical trial
bull Stewart DJ1 Kurzrock R bull BMC Cancer 2013 Apr 1613193 doi 1011861471-2407-13-193
13
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
Tumor Type Braf Kras EGFR PIK3CA NRAS cKit GNA11
GNAQGNAS
Lung amp Bronchus 3 31 13 4 0 0 0 0 Colon 9 39 1 21 5 1 0 2 Pancreatic 1 82 1 2 0 0 1 2 Melanoma 34 2 0 1 20amp 2 0 0 GEGastric 1 5 1 4 0 0 0 0 Kidney 2 1 0 4 0 0 0 0 Leukemia amp Lymphoma 1 3 4 0 6 0 0 0 Prostate 1 2 0 9 2 2 0 0 Breast 0 1 1 27 0 0 0 0 Ovarian 1 8 1 6 1 0 0 0
Frequency () of Mutations In Common Cancers
Mutations determined by Cobas Sanger and or Illumina NGS n le 100 ampAscierbo et al Lancet 14249-56 2013
Gatalica et al ASCO 2013
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
FORWARD GENOMIC ONCOLOGY
gt60 tumor Tumor Biopsy
Sequencing amp Analysis
Buccal swab or
Blood (germline)
Sequencing Tumor Board
Disclosure of Results Genetic Counselor
1) Actionable 2) Incidental
Informed Consent amp
Genetic Counselor
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
FoundationOnetrade Report
Summary of results and genomic alterations identified
Targeted therapies and clinical trials that may be relevant based on genomic alterations identified
Patient and ordering physician information
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
TheraLink Results on Initial Biopsy
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
Blue Downregulated amp CNV Loss Red Upregulated amp CNV Gain
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
Recommended Treatment SEQUENCING PROGRESS NOTE
History of present illness Wanda is a 71 yo with history of stage IIIC ovarian cancer Treatment Recommendations AKT2 amplication- no approved therapies Clinical trials of Akt inhibitors for various tumor types mTOR inhibitors everolimus and temsirolimus are FDA approved for other indications PIK3CA ndash mTOR inhibitors everolimus and temsirolimus are FDA approved for other tumor types Associated with resistance to Egfr-targeted therapies CCNE1 amplification ndashprimary resistance to platinum-based treatment in patients with ovarian carcinoma MYC amplification ndash Preclinical evidence suggests may be more sensitive to 5-fluorouracil (5fu) and paclitaxel Our treatment recommendation for this patient would be Taxol +- 5Fu with Everolimus We thank you again for the referral and working with us Sincerely Dr Brian Leyland-Jones and team Avera Medical Group Genomic Medicine
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
Darwin and cancer branched evolution
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
mTOR active in all primary regions except R4 and metastases
On
Off
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull As of Sep 2015More than 200 patients with breast or gynecology cancer were referred to our MEM group
bull A committed result was suggested by the clinical
outcome of the patients on MEM suggested drugs
bull We have clinical outcome from patients on MEM therapy for up to 24 months
bull Clinical outcome were collected on 74 patients
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
bull Almost 60 of patients on MEM therapy have responded positively (Complete response or partial response)
bull More than 80 of the patients got their disease under control
bull Disease only progressed in 19 of the patients Best Clinical Outcome Count
Complete Response 19 Partial Response 27 Stable 17 Progressed 11 TOTAL 74
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
ldquohellip patients who benefit from chemotherapy (in the metastatic setting) may be treated successfully with other regimens at the time of progression However the chance of response decreases by about half with each subsequent treatmentrdquo DeVita VT Cancer Prin amp Prac of Oncol 5th Edition pp 1605
Graph was NOT taken from DeVita but is provided to illustrate the effects of the quote above and assumes an initial response of 60
Probability of Response By Line of Therapy
010203040506070
0 1 2 3 4 5+
Number of Prior Regimens
Probability of Response
Likelihood of Response by Extent of Prior Treatment
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
Cancer Progress by Defined Health New York NY | March 17-18 2015
TIMELINE
Neoadjuvant Treatment
Surg
ery
Base
line
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Tumour Biopsy
Cores 1-2 FFPE+ 5 FROZEN
Neoadjuvant B ios pec imens C ollec tion
3 w
eeks
SerumPlasma Whole blood
SerumPlasma
SerumPlasma
Start Treatment Other Cycles
MRI Ki67
MRI Ki67
MRI
SCREENING
Eg CTPET MUGAECHO
+ CONSENT
9 w
eeks
Evaluation (at Clinicianrsquos discretion)
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-
1 MULTIPLATFORM 2 COMBINATIONS OF THERAPIES (SOME OF
WHICH HAVE NEVER BEEN COMBINED BEFORE) N OF ONE
3 SHIFT TO EARLY TREATMENT
4 THE NEXT GENERATION OF CUTTING EDGE THERAPIES ARE ALL IN CLINICAL TRIALS BUILDING THE DRUG UMBRELLA
5 REGULATORY AUTHORITIES 6 RE-EDUCATIONhelliphellipNCCN GUIDELINES 7 INSURANCE COVERAGE TESTING DRUGS
bull Patients that live longer cost more
THE CHALLENGEShellip
- Precision Medicine Lessons from meta-analyses of 70253 patients
- Meta-Analyses Conducted 1) Trials leading to FDA approval from trastuzumab (1998) until June 2013 38104 patients 112 trials 2) Phase II studies published between 2010 through 2012 32149 patients 570 trials
- Slide Number 3
- Slide Number 4
- Slide Number 5
- Slide Number 6
- Slide Number 7
- Slide Number 8
- Slide Number 9
- Slide Number 10
- PRECISION ONCOLOGY
- Slide Number 12
- NEW TRIAL DESIGNS
- Slide Number 14
- Slide Number 15
- Slide Number 16
- FoundationOnetrade Report
- Slide Number 18
- TheraLink Results on Initial Biopsy
- Slide Number 20
- Recommended Treatment
- Darwin and cancer branched evolution
- mTOR active in all primary regions except R4 and metastases
- Slide Number 24
- Slide Number 25
- Likelihood of Response by Extent of Prior Treatment
- Slide Number 27
- Neoadjuvant Biospecimens Collection
- Slide Number 29
-