immunotherapy in gynaecological cancers -...
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Immunotherapy for Gynaecological (Breast and
Ovarian) CancersESMO Immunotherapy Preceptorship
Singapore 2017
David SP Tan, MD PhD FRCP
Consultant Medical Oncologist
National University Cancer Institute, Singapore
Targeting the Cancer Immunity Cycle
Chen and Mellman. Immunity 2013
Salgado et al Ann Oncol. 2014;26(2):259-271. doi:10.1093/annonc/mdu450
Goodman et al Mol Cancer Ther; 16(11) November 2017
ORRLow to intermediate TMB: 20%High TMB: 58% Multivariate p<0.001Median PFS: Low to intermediate TMB: 3.3mthsHigh TMB: 12.8 mthsMultivariate p<0.001Median OS:Low to intermediate TMB: 16.3 mthsHigh TMB: Not reachedMultivariate p=0.036
Tumour mutational burden in Gynaecological Cancers
Zehir et al Nature Medicine 2017
Ovarian ca subtype specific TMB: some hot some not?Chalmers et al. Genome Medicine (2017) 9:34: Analysis of 100,000 human cancer genomes
Immunotherapy in Breast Cancer
Lymphocyte predominant breast ca
Intra-epithelial TILs
(~10%)
Stromal TILs (sTILs)~80%
Modified from Adams et al JCO 2014
Primary TNBC
sTILs in breast ca subtypes
sTILs and outcomes in adj breast ca
trials
Loi et al Nature Reviews Cancer
2016
sTILs are prognostic and predictive of neoadjuvant
chemoresponse
Vanderbilt MD Anderson Institut de Cancérologie
Pathway analysis overlap:
Subset of TNBC across all profiles - altered immune checkpoint gene regulation
Le Du F Oncotarget. 2015
Molecular Subtypes of TNBC
TNBC ER positive
Mutation rate higher in TNBC compared to other subtypes
Luminal ALuminal BHER2BasalNormal
SynonymousNonsynonymous
10
8
6
4
0
2
No
. mu
tati
on
s/M
bSomatic mutations in breast cancer subtypes
Tumour mutation burden in breast cancers
Banerji S, et al. Nature. 2012;486(7403):405-409.
TNBC is most immunogenic breast ca
Salgado et al Ann Oncol. 2014;26(2):259-271
Pembrolizumab(n = 32)
Atezolizumab (n = 71)
Avelumab(n=58 /9)
Target PD-1 PD-L1 PD-L1
Tumour PD-L1 ≥1% (58%+) ≥5% All / ≥1%
ORR 18.5% 13% 8.6% / 44.4%
SD 25.9% 18% 22.4%
Immune Checkpoint inhibitors in Metastatic TNBC
Nanda et al. JCO 2016, Schmid et al. AACR 2017, Dirix et al SABCS 2015
Immune checkpoint inhibitors have shown durable responses in heavily pretreated patients with metastatic TNBC
Pembrolizumab in TNBC (n=32)PD-L1+ tumours: PD-L1 expression on tumour cells (>1%) (58% PD-L1+)
Nanda et al. SABCS 2014
Keynote-012: Pembrolizumab in TNBC Best Response
100
80
60
40
20
0
-20
-40
-60
-80
-100
Ch
ange
fro
m b
asel
ine
in s
um
of
lon
gest
dia
met
er o
f ta
rget
lesi
on
(%
)
Confirmed complete response (nodal disease)Confirmed partial responseStable diseaseProgressive disease
Objective response rate: 18.5%Stable disease: 25.9%Median DOR: not reached3 of 5 responding for more than 11mths
Schmid P, et al. AACR 2017
Atezolizumab in TNBC
Criteria MedianDOR
(range)
Median PFS
(95% CI)
RECIST v1.1
21.1 mo(2.8 to 26.5+)
1.4 mo(1.3, 1.6)
irRC 21.1 mo(2.8 to 33.9+)
1.9 mo(1.4, 2.6)
Overall TNBC cohort
Patients With RECIST v1.1 Response or Stable Disease
or irRC Response
irPRa
irPRairPR
irPR
Usual median OS in this population ~ 12 months.
Study KEYNOTE-086 Cohort A, Adams, S. et al. ASCO 2017
Patients
• Age ≥18 y
• Centrally confirmed TNBCa
• ≥1 prior systemic
treatment for mTNBC with
documented PD
• ECOG PS 0-1
• LDH <2.5 x ULN
• Tumor biopsy sample for
PD-L1 evaluation
• No radiographic evidence
of CNS metastases
• Measurable disease per
RECIST v1.1 by central
review
Pembrolizumab
200 mg IV Q3W
for 2 years or until PD,
intolerable toxicity,
patient withdrawal, or
investigator decision
• Primary end points: ORRb and safety• Secondary end pointsb: DOR, DCR,c PFS, OS
N = 170
Protocol-specified
follow-up
Best Overall Response (RECIST v1.1, Central Review)
Total
Populationa
N = 170
PD-L1 Positive
n = 105
PD-L1 Negative
n = 64
ORR, n (%) [95% CI] 8 (4.7) [2.3-9.2] 5 (4.8) [1.8-10.9] 3 (4.7) [1.1-13.4]
DCR,b n (%) [95% CI] 13 (7.6) [4.4-
12.7]
10 (9.5) [5.1-
16.8]
3 (4.7) [1.1-13.4]
Best Overall Response, n
(%)
Complete response 1 (0.6) 1 (1.0) 0
Partial response 7 (4.1) 4 (3.8) 3 (4.7)
Stable disease 35 (20.6) 22 (21.0) 12 (18.8)
Progressive disease 103 (60.6) 66 (62.9) 37 (57.8)
Not evaluablec 5 (2.9) 2 (1.9) 3 (4.7)
Not able to be assessedd 19 (11.2) 10 (9.5) 9 (14.1)
0 2 4 6 8 1 0 1 2 1 4 1 6
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
T im e , m o n th s
OS
, %
N o . a t r is k
8 8 8 8 8 4 0 0
35 35 35 33 29 16 1 0
1 0 3 94 72 63 39 20 1 0
9
2
7
4
Overall Survival by Best Overall Response
100%100%64.6%
100%89.6%39.0%
Events/P
ts, n
Median
(95% CI)
CR or
PR0/8
Not reached
(NR-NR)
SD 6/35Not reached
(12.7-NR)
PD 66/1037.1 mo
(6.3-8.8)
Exploratory Analysis
KEYNOTE-086 Cohort B: Study DesignAdams S et al. ASCO 2017
Patients• Age ≥18 years• Centrally confirmed mTNBCa
• No prior systemic therapy for metastatic disease
• ECOG PS 0-1• LDH <2.5 x ULN• PD-L1 CPS ≥1%• No radiographic evidence of
CNS metastases• Measurable disease per
RECIST v1.1 by central review
Pembrolizumab 200 mg IV Q3W
for 2 years or until PD, intolerable toxicity, patient withdrawal, or investigator
decision
N = 84Protocol-specified follow-up
• Primary end points: safety• Secondary end points: ORR, DCR,b DOR, PFS, OS
Pembrolizumab Antitumor Activity in Previously Treated and Previously Untreated mTNBC
Cohort A (N = 170): Previously Treated,
Regardless of PD-L1 Expression
Cohort B (N = 52)1: Previously Untreated,
PD-L1 Positive
0
4
8
12
16
20
24
28
32
36
40
OR
R, %
0
4
8
12
16
20
24
28
32
36
40
OR
R, %
23.1%
Complete response
Partial response
Total PD-L1Positive
PD-L1Negative
Total(All PD-L1 Positive)
Stable disease≥24 wk
4.7%
9.5%7.6%
KEYNOTE-086: sTIL Level and Tumor Response in mTNBC
Loi S, et al. ESMO 2017. Abstract LBA13.
Median sTIL, % (IQR) P Value
Combined cohorts▪ Responder (n = 18)▪ Nonresponder (n = 175)
37.5 (8.75-66.25)5 (2-15)
< .001
Cohort A▪ Responder (n = 7)▪ Nonresponder (n = 140)
10 (5-30)5 (1-10)
.062
Cohort B▪ Responder (n = 11)▪ Nonresponder (n = 35)
50 (35-70)15 (5-40)
.009
▪ sTIL level, cohort, and LDH level were independent predictors of tumor response to pembrolizumab
Pembrolizumab Antitumor Activity in Previously Treated and Previously Untreated mTNBC
Cohort A (N = 170): Previously Treated,
Regardless of PD-L1 Expression
Cohort B (N = 52)1: Previously Untreated,
PD-L1 Positive
0
4
8
12
16
20
24
28
32
36
40
OR
R, %
0
4
8
12
16
20
24
28
32
36
40
OR
R, %
23.1%
Complete response
Partial response
Total PD-L1Positive
PD-L1Negative
Total(All PD-L1 Positive)
Stable disease≥24 wk
4.7%
9.5%7.6%
Do immune check point
inhibitors work better earlier in
the course of disease?
Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab plusChemotherapy vs Placebo plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for TNBC (KEYNOTE-522)
TNBCT2 or N+
ER/PR < 1%N=855
2Surgery
Surgery
Primary end pointspCR and EFS
Secondary end point OS
carboplatin (AUC5 q3w or AUC1.5 qw) x 4 cycles
Stratification factors: Nodal status ,Tumor size, Choice of Carboplatin dose/schedule
1
Pembro 200 mg q3w
Placebo q3w
AC/EC x 4Pembro 200 mg
q3w X 9 cycles
carboplatin (AUC5 q3w or AUC1.5 qw) x 4 cycles
AC/EC x 4Placebo q3w X
9 cycles
wPaclitaxel x 4 cycles
wPaclitaxel x 4 cycles
Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1 (NeoTRIPaPDL1)
Surgery
Primary Endpoint
5 year Event Free Survival
Secondary Endpoints
pCR
Clinical Objective Response
Distant Event Free Survival
Safety and tolerability
AC/EC/FEC
x 4 cycles
TNBCER/PR < 1%
Stage III N=272
Randomized phase III
Carboplatin (AUC 2 D1,8 q3w)
q3w x 8 cycles
Atezolizumab 1200 mg q3w
x 8 cycles
nab-paclitaxel 125 mg/m2 D1, 8
q3w x 8 cycles
Carboplatin (AUC 2 D1,8 q3w)
q3w x 8 cycles
nab-paclitaxel 125 mg/m2 D1, 8
q3w x 8 cycles
Combination Immune-and Chemotherapy in TNBC
Nab-Paclitaxel + anti-PD-L1 (atezolizumab)
Adams S, SABCS 2015; Tolaney, S SABCS 2016, ESMO 2017
2nd/≥3rd line Patients
1st line Patients
All1st line (n=17)
2nd/3rd L (n=18)
ORR 34.4% 41.2% 27.3%
CBR 40.6% 47.1% 36.4%
Eribulin + anti-PD-1 (pembrolizumab)
Independent of PD-L1 status
IMpassion130: Atezolizumab in 1st line mTNBC
Central testing forPD-L1 status
Patients with incurable advanced/
metastatic TNBC (N=900)
R1:1
Surv
ival
Fo
llow
-Up
Study treatment phase
Un
til P
D
Stratification: • Tumour tissue PD-L1 expression
(IHC 0 vs IHC 1,2,3)• Liver metastases (Yes vs No)• Prior taxane treatment (Yes vs No)
Un
til l
oss
of
Clin
ical
Ben
efit
Placebo + nab-paclitaxel (100mg/m2 qw)
Atezolizumab (840mg q2w) + nab-paclitaxel (100mg/m2 qw)
KN-355: Randomized Phase III of Pembrolizumab + Chemo
vs Placebo + Chemo in 1st line mTNBC
#Treatment may be continued
until confirmation of PD
N=828
▪Previously untreated locally recurrent inoperable or metastatic TNBC▪Central determination of TNBC and PD-L1 ▪No active CNS metastases
Pembrolizumab + Chemotherapy*
Placebo**
+ Chemotherapy*
Protocol-Specified
Follow-Up
Progressive Disease#/Cessation of Study
Therapy2:1
*Paclitaxel, nab-paclitaxel or
gemcitabine/carboplatin**Normal saline
Primary Endpts➢ PFS in all subjects
and PD-L1-positive
➢ OS in all subjects and PD-L1-positive
2nd Endpoints➢ ORR, DCR, DOR in
all subjects and PD-L1-positive
➢ Safety
Summary of IO studies in breast caTNBC
ER+ve
Loi et al NRC 2016
Summary of status of breast cancer immunotherapy investigational trials, by phase.
Robert H. Vonderheide et al. Clin Cancer Res
2017;23:2640-2646
Natural Killer Cell Therapy - HER2 Basket Study
Trastuzumab + Natural Killer cell therapy for all HER2 amplified/ IHC 3+ tumours Currently recruiting
Dario Campana Lee Soo Chin
Immunotherapy for Ovarian Cancer
Potential Cellular Origins of Ovarian Cancer Subtypes
Prat J Ann Oncol 2012
Ovarian Cancer: Different subtypes = Different Origins = Different Molecular
Abnormalities
Role of Immune Cells in Ovarian Cancer
• OC is an immunogenic
tumour1-4
– Strong immunosuppressive
environment present in OC
– Spontaneous antitumor immune
response can be detected in the
form of tumor-reactive T cells
and antibodies
• Analyses of OC patient
samples showed presence of
intratumoral T cells was
associated with better clinical
outcome4
1. Turner TB et al. Gynecol Oncol. 2016;142:349-356. 2. Coukos G et al. Ann Oncol. 2016;27(suppl 1):i11-i15. 3.
Mandai M et al. Int J Clin Oncol. 2016;21:456-461. 4. Zhang L et al. N Engl J Med. 2003;348:203–213.
Ove
rall
Su
rviv
al
(%)
Month
0
25
50
75
100
0 12 24 36 48 60 72 84 96 108 120 132
P<0.001
Intratumoral T cells
No intratumoral T cells
Classification of tumours based on TILs and PDL1 expression
Teng et al Cancer Res; 75(11) June 1, 2015
EOC Histotype and Tumour MicroenvironmentWebber et al Gynecol Onc 2016
Taube et al 2014Smyth et al 2016
Heong et al J Gynecol Oncol. 2017
Immune Checkpoint Inhibitors in Ovarian Cancer
Responses in unselected EOC only ~10-15%
Avelumab (PD-L1 inhibitor) in EOC: Response by subgroup
Unconfirmed ORR by RECIST 1.1
n (%) 95% CI
Tumor burden (median sum of longest diameter=58 mm)
> median (n=35) 2 (5.7%) (0.7, 19.2)
≤ median (n=40) 6 (15.0%) (5.7, 29.8)
# of prior treatment lines for locally advanced or metastatic disease, excluding adjuvant therapy
≥3 (n=51) 4 (7.8%) (2.2, 18.9)
2 (n=10) 1 (10.0%) (2.5, 44.5)
≤1 (n=14) 3 (21.4%) (4.7, 50.8)
Platinum resistance/sensitivity*
Resistant (<6 month PFI; n=44) 4 (9.1%) (2.5, 21.7)
6-12 month PFI (n=18) 2 (11.1%) (1.4, 34.7)
Sensitive (>12 month PFI; n=10) 2 (20.0%) (2.5, 55.6)
* Defined based on platinum-free interval (PFI) since last line of platinum:<6 months, 6-12 months, and > 12 months; PFI could not be determined for 3 patientsDisis et al ASCO 2015
Earlier use in platinum sensitive disease better?
First Line Avelumab + Chemo: JAVELIN 100
B9991010
Observation
Avelumab Q2W
Chemotherapy
Chemotherapy
Chemotherapy Maintenance
Chemotherapy + Avelumab Q3W
Avelumab Q2W
RANDOMIZATION
Arm A
Arm B
Arm C
Eligibility Criteria• Previously untreated• Stage III-IV• Prior debulking surgery or plan for neoadjuvant chemotherapy • ECOG PS 0 or 1• Mandatory archival tissue
Chemotherapy: Choice of carboplatin + q3w, paclitaxel, OR carboplatin + weekly paclitaxelMaintenance avelumab up to 24 months
n = ~951 (388 PFS events) 272 events within each of the 2 main comparisons
Primary endpoint:
PFS from randomization (A vs B, A vs C)
Secondary endpoints:
Maintenance PFS, OS, ORR, duration of response, pCR, PFS2, PROs, safety, PK
Patients whose tumor was not progressing as per RECIST 1.1 criteria (CR, PR, or SD) will be allowed to continue onto the maintenance portion of the study
ClinicalTrials.gov Identifier:NCT02718417
First Line Atezolizumab and bevacizumab
IMaGYN050 Study Design: Primary Surgery Cohort
Stratification variables:• Stage/debulking status• GOG PS• PDL1 IC 0 vs IC1+• Adjuvant/Neo-adjuvant
Paclitaxel 175 mg/m2 Q3wk
Carboplatin AUC 6 Q3wk
Carboplatin AUC 6 Q3wk
Paclitaxel 175 mg/m2 Q3wk
R
1:1
• Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer
• Stage III (sub-optimal/ optimal w/ macroscopic residual), Stage IV, or patients w/ advanced disease treated in the neo-adjuvant setting
• GOG PS 0-2
PL q3w X 22 cycles
Atezo 1200mg q3w x 22cycles
No cross-over
Co-Primary endpoint: PFS &OS in all comers and Dx+ (IC 1+)
Bev 15 mg/kg Q3wk
Bev 15 mg/kg Q3wk
Bev 15 mg/kg X 16 cycles
Bev 15 mg/kg X 16 cycles
Double blinded, 1:1 randomized, placebo-controlled multi-center study
ClinicalTrials.gov Identifier: NCT03038100
Platinum sensitive recurrent EOC
Platinum resistant disease: Phase 3
Combination IO + PARP inhibitor / VEGFR inhibitor
IO agent Disease status Phase N Result G3/4 Adverse events
Durvalumab + olaparib
Recurrent EOC I/II 10 PR (1;11+mths)SD (7;4+mths)
Lymphopenia,anemia
Durvalumab + cediranib
Recurrent EOC I/II 4 PR (1;7mths)SD (2;1 for 6mths)
Lymphopenia, anemia, nausea,
pulmonary hypertension,
PE, hypertension,
fatigue, headache
Lee J, J Clin Oncol. 2016:34(suppl; abstr 3015)
Ongoing studies of Immune
checkpoint inhibitors in
ovarian cancer
Gaillard et al. Gynecologic Oncology Research and Practice (2016) 3:11
But many questions….
• How to select EOC patients?
– single vs combo?
• Biomarkers?
• Optimal combinations?
• Timing of treatment?
– First line/ plat sens recurrence/ plat resistant disease?
Will ongoing studies answer these questions???
Epi-AMesStem-AStem-B
Epi-B
Mesenchymal
IFN-inducibleMHC Class IIIgs
Stem-A
Epi-A/Stem
Epithelial
VCAM1
ZEB1
FN1
PDGFRA
TWIST1
OAS1/2
HLA-Ds
IGH/K/Ls
MYCN
CDH3/2
NCAM1
TOP2A/BUB1/CCNE1/CENPA
LGR5
WNT5A
DKK3
SFRP1
PROM1
XIST
KRT6A/17/14/19/7
EPCAM
CD24
CDH1
MUC1
Epi-A
Epi-B
Mes
Stem-A
Stem-B
p < 0.0001
Molecular subgroups of EOC e.g. Epithelial/ C2/ Immunoreactive,
Mesenchymal/C1 , or Stem-like/ C5/ Proliferative with distinct survival
outcomes.
Are EOC Gene expression molecular subtypes helpful?
Tan, Miow & Huang et al., EMBO Mol Med, 2013
❖ Meta-analysis (Tan, Miow, &
Huang et al., EMBO MM, 2013) of
1,538 EOCs including all
histological types.
4 subtypes showing survival
differences
Molecular subtypes likely to reflect aggregate phenotype of tumour cells & microenvironmental factors
Balkwill et al Journal of Cell Science, 2012
Outcome of ‘immune’ and ‘proangiogenic’
groups of ovarian cancer in ICON 7
Bev had adverse
effect on PFS in
immune
subgroup
Benefit in pro-
angiogenic
subgroup
Control arm
ICON7
Immune and
proangiogenic
groups
Gourley et al ASCO 2014
EpiB/ C2 (immunoreactive) subtype for immunotherapy?
C2 = immuno-reactive mol. subtype
EpiB / C2 (immunogenic) subtype: The Shirley Pepke Story
3/3 responses to PD1/PDL1 inhibitor in ovarian clear cell cancer(OCCC)
Disis et ASCO 2015 Hamanishi et al JC 2015
Baseline: 69 mm RLL lesion Week 25: 41 mm (-40.6%)
Are PDL1/PD1 inhibitors more likely to work in OCCCs?
Avelumab2/2 OCCC responses
Nivolumab1/1 OCCC response -CR
The Emerging Molecular Landscape of OCCCs
Tan et al BJC 2013
Upregulation of IL6 in OCCC: a marker of tumour inflammation
IL-6
Anglesio et al CCR 2011
Huang CCR 2007
High IL-6(H score ≥150)
PD-L1 +ve(PD-L1 ≥ 1%)
PD-L1 –ve(PD-L1 < 1%)
Low IL-6(H score < 150)
OCCC IL6 and PD-L1 expression, n=103: Courtesy of Dr D. Lim
86% 14%
17% 83%Diana Lim et al (unpublished)
Chandler et al Nature Comm 2015
ARID1A and PIK3CA mutations cooperate to promote tumour growth
through sustained IL-6 overproduction.
0 5 0 1 0 0 1 5 0
0
5 0
1 0 0
M o n t h
Pe
rc
en
t s
ur
viv
al
ClinicaloutcomesbasedonOCCCirGESsubtypes
P=0.0864
OverallSurvival(n=74)
Overallsurvival(%
)
Recurrence-FreeSurvival(n=74)
0 5 0 1 0 0 1 5 0
0
5 0
1 0 0
M o n t h
Pe
rc
en
t s
ur
viv
al
Recurrencefreesurvival(%
)
G1
G2
G3
G4
G1
G2
G3
G4
P=0.0284
Months
Months
OCCC gene expression subtypes
Heong et al ESMO 2017
74 OCCCs using nanoString nCounterPanCancer Immune Profiling Panel
G1 (NK cell and PD-1
enriched) and
G2 (CTLA-4 high)
subgroups of OCCC
associated with
worse outcomes
Clinical Responses
to PD-1 inhibitor
pembrolizumab in
MMR deficient vsproficient cancers
Le DT et al. N Engl J Med 2015;372:2509-2520
Best response to pembrolizumab in MSI-H non-colorectal tumours
Diaz et al ASCO 2016
• Ovarian cancers developed at mean 48 years of age
• FIGO stage I in 47% of cases
• Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented.
• The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%.
• IHC loss of the corresponding MMR protein in 92% of tumors
Gynecologic Oncology 121 (2011) 462–465
OCCC: a genetically inherited disease?
A Multicentre Phase II randomised trial of MEDI4736 (DURVALUMAB) versus physician’s choice chemotherapy in
recurrent ovarian clear cell adenocarcinomas (MOCCA)
Relapsed Clear Cell
Cancer Ovarian Cancer
(>70% clear cell)
Inclusion
-Histologically confirmed
- WT1 negative
-Relapsed after at least 1
line of platinum-based
chemotherapy
-Measurable disease by
RECIST 1.1
-ECOG 0 / 1
Exclusion
-Concurrent use of
experimental anti-cancer
agent
-Untreated brain mets
MEDI-4736
(Durvalumab)
1500mg 4 weekly
for max. 24mths
CAELYX or
Investigator’s choice if
prior Rx included caelyx
(but antiangiogenic
therapy not permitted)
Crossover
on PD
2:1
randomisation
2
1
Singapore (GOGS)
Korea (KGOG)
Australia (ANZGOG)
N = 31
N = 15
Endpoint: PFS
What’s next for Immunotherapy in Gynae Cancer
Cold to hot immunologic conversion
Robert H. Vonderheide et al. Clin Cancer Res
2017;23:2640-2646
Immunotherapy combinations
Heong et al J Gynecol Oncol. 2017 Mar;28(2):e20.
Phase I study of Combined Medi4736 (Durvalumab, PD-L1 inhibitor), PARP inhibitor (Olaparib), and AKT inhibitor
(AZD5363) in Solid Tumours (MediPAC Study)
Funded by NMRC IAF GrantPI: David Tan
All comer Solid
Tumours
Recruiting from 1st quarter 2018
Journal of Thoracic Oncology, 2017 Vol. 12 No. 5
Can the gut microbiome boost immunotherapy?
Snyder et al Science 2015Science, 27 NOVEMBER 2015 • VOL 350 ISSUE 6264
Summary: Immunotherapy in Breast & Ovarian Cancers
• Specific subtypes are immunogenic – TNBC, OCCC, MSI-H/ MSI
• Immune checkpoint inhibitors effective as single agent is small proportion of unselected patients ~10-15%
• Combination strategies being explored
• Additional immunotherapy modalities e.g. adoptive cellular therapy, being explored
• Biomarkers crucial e.g.?cancer immunogram, ?gut microbiota, ?gene expression– Guide optimal combination of immunotherapy modalities
– Guide timing and selection of agents in patients
THANK YOU
Acknowledgements:Rebecca Dent (My breast friend)National Cancer Centre, Singapore