cco gi cr 2013 slides
TRANSCRIPT
January 24-26, 2013San Francisco, California
Gastrointestinal CancersCCO Independent Conference Coverageof the 2013 Gastrointestinal Cancers Symposium*
This program is supported by an educational grant fromThis program is supported by educational grants from
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
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About These Slides
� In the following slides, you will find highlights of the key studies from this meeting. Be sure to review the slide notes field for each slide for insightful commentar y from our expert faculty
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DisclaimerThe materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
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Faculty
Al B. Benson III, MD, FACPProfessor of Medicine, Department of MedicineDivision of Hematology/Oncology, Feinberg School of MedicineAssociate Director for Clinical InvestigationsRobert H. Lurie Comprehensive Cancer CenterNorthwestern UniversityChicago, Illinois
Thomas H. Cartwright, MDCo-Chairman, US Oncology GI ResearchUS Oncology/Ocala OncologyOcala, Florida
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Disclosures
Al B. Benson III, MD, FACP, has disclosed that he has received consulting fees from Bayer, Celgene, Genentech, Genomic Health, and Sanofi, and funds for research support from Amgen, Astellas, Bayer, Genentech, and Gilead Sciences.
Thomas H. Cartwright, MD, has disclosed that he has received consulting fees from Amgen, Bayer, Bristol-Myers Squibb, and sanofi-aventis and has received fees for non-CME/CE services received directly from a commercial interest or their agents (e.g., speakers’ bureaus) from Amgen, Bayer, Bristol-Myers Squibb, and Genentech.
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Overview
� Colorectal Cancer– First-line Bev + FOLFIRI or
FOLFOXIRI in mCRC
– First-line Capecitabine ± Bev in Elderly mCRC Pts
– First-line Bev + Chemo ± Erlotinib in Unresectable mCRC
– Pegfilgrastim vs Placebo After First-line Chemo + Bev in Adv. CRC
– First-line mFOLFOX6 + Panitumumab or Bevacizumab in mCRC
– Biomarkers and Response to Regorafenib in mCRC
– Stage II Colon Cancer: Adding Recurrence Score and MMR Status to Risk Assessment
� Esophageal and Stomach Cancer– Docetaxel vs ASC in
Esophagogastric Cancer
– BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer
� Pancreatic Cancer– Gem- or Cape-Based CRT in
Locally Advanced Pancreatic Cancer
– Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer
– Adjuvant Gem vs S-1 in Resected Pancreatic Cancer
– GTX in Patients With Metastatic Pancreatic Cancer
– pCR, nCR Rates After Chemo + SBRT in Borderline Resectable Pancreatic Cancer
Colorectal Cancer
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Phase III TRIBE Trial: First-line Bev + FOLFIRI or FOLFOXIRI in mCRC
� Primary objective: PFS
� Secondary endpoints: OS, safety, R0 resection, biomarkers
Loupakis F, et al. ASCO GI 2013. Abstract 336.
Patients with unresectable mCRC,
no previous chemotherapy for advanced disease
(N = 508)
Maintenance with 5-FU + bevacizumab
until PD
FOLFIRI* +Bevacizumab 5 mg/kg
(n = 256)
FOLFOXIRI† +Bevacizumab 5 mg/kg
(n = 252)
*FOLFIRI: irinotecan 180 mg/m2, leucovorin 200 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2400 mg/m2 over 48 hrs, q2w†FOLFOXIRI: irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, 5-FU infusion 3200 mg/m2 over 48 hrs, q2w
Max 12 cyclesStratified by PS (0-1 vs 2), center,
previous adjuvant chemo
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TRIBE Trial of First-line Bev + FOLFIRI or FOLFOXIRI in mCRC: PFS
Loupakis F, et al. ASCO GI 2013. Abstract 336.
Follow-up Time (Mos)
FOLFOXIRI + Bev
FOLFIRI + Bev
Median follow up: 26.6 mosFOLFIRI + Bev: n = 256/progressed = 225FOLFOXIRI + Bev: n = 252/progressed = 199
Pts at Risk, nFOLFIRI + Bev 256 198 93 42 22 10 3 0 0 0FOLFOXIRI + Bev 252 203 125 64 27 15 8 3 1 0
Pro
babi
lity
of P
FS
1.0
0.8
0.6
0.4
0.2
0
0.9
0.7
0.5
0.3
0.1
0 6 12 18 30 42 5424 36 48
FOLFIRI + Bev, median PFS: 9.7 mosFOLFOXIRI + Bev, median PFS: 12.2 mosUnstratified HR: 0.73; P = .0012Stratified HR: 0.71; P = .0006
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TRIBE Trial of First-line Bev + FOLFIRI or FOLFOXIRI in mCRC: Response Rates
Loupakis F, et al. ASCO GI 2013. Abstract 336.
Tumor shrinkage superior with FOLFOXIRI
Best Response, %FOLFIRI + Bev
(n = 256)FOLFOXIRI + Bev
(n = 252)P Value
Best response 3 4
PR 50 61
Response Rate 53 65 .006
SD 32 24
Progressive disease 5 2
Not assessed 10 9
FOLFOXIRI + Bev
FOLFIRI + Bev
% C
hang
e F
rom
Bas
elin
e
80
60
40
20
0
-20
-40
-60
-80
-100
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TRIBE Trial of First-line Bev + FOLFIRI or FOLFOXIRI in mCRC: Safety
Loupakis F, et al. ASCO GI 2013. Abstract 336.
Compared with FOLFIRI + Bev, FOLFOXIRI + Bev increased the incidence of grade 3/4 stomatitis, diarrhea, and neutropenia, but not febrile neutropenia, serious AEs, or treatment-related deaths
Grade 3/4 AE, %
FOLFIRI + Bev
(n = 254)
FOLFOXIRI + Bev
(n = 250)P Value
Nausea 3 3 1.000
Vomiting 3 4 .492
Diarrhea 11 19 .012
Stomatitis 4 9 .048
Neutropenia 20 50 < .001Febrileneutropenia 6 9 .315
Neurotoxicity 0 5 < .001
Hypertension 2 5 .157Venous thrombosis 6 7 .593
Arterial thrombosis 2 1 1.000
Bleeding 1 1 1.000
Event, %FOLFIRI
+ Bev(n = 254)
FOLFOXIRI + Bev
(n = 250)
Serious AEs 19.7 20.4
Fatal AEs 3.5 2.8
Treatment-related deaths
1.6 2.4
Early deaths(within 60 days from randomization)
2.7 3.6
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Phase III AVEX Trial: First-line Capecitabine ± Bev in Elderly mCRC Pts
� Primary objective: PFS
� Secondary endpoints: OS, ORR, DOR, time to response, safety
Cunningham D, et al. ASCO GI 2013. Abstract 337.
Patients aged 70 yrs or older, eligible for
single-agent chemotherapy, no
previous chemo for mCRC or adjuvant anti-VEGF therapy
(N = 280)
Capecitabine 1000 mg/m2 BID on Days 1-14 q3w
(n = 140)
Capecitabine 1000 mg/m2 BID on Days 1-14 q3w +
Bevacizumab 7.5 mg/kg q3w(n = 140)
Stratified by ECOG PS (0-1 vs 2), region
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AVEX Trial of First-line Capecitabine ± Bev in Elderly mCRC Pts: PFS
Cunningham D, et al. ASCO GI 2013. Abstract 337.
Pro
port
ion
Pro
gres
sion
Fre
e
Mos
Cape (n = 140)
Cape + Bev (n = 140)
Pts at Risk, nCape 140 121 99 80 68 55 41 28 23 16 13 9 8 3 2 2 2 2 1 0 0Cape + Bev 140 109 82 56 38 25 13 9 6 4 4 2 1 1 1 1 1 1 1 1 0
HR: 0.53 (95% CI: 0.41-0.69;P < .001)
1.0
0.8
0.6
0.4
0.2
0
0 4 8 12 20 28 4016 24 342 6 10 14 22 30 3218 26 36 38
5.1 mos 9.1 mos
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AVEX Trial of First-line Capecitabine ± Bev in Elderly mCRC Pts: ORR and AEs
Cunningham D, et al. ASCO GI 2013. Abstract 337.
Outcome, %Cape + Bev
(n = 140)Cape
(n = 140)
ORR (CR + PR) 19.3 10.0
P = .042
� CR 2.1 1.4
� PR 17.1 8.6
SD 55.0 47.9
PD 10.0 21.4
Disease control rate (CR + PR + SD)
74.3 57.9
P = .005
AE, %Cape + Bev
(n = 134)Cape
(n = 136)
Any AE 95.5 95.6
SAE 30.6 32.4
Grade ≥ 3 AE 59.0 44.1
Grade 5 AE 8.2 11.8
Any AE leading to dose modification
54.5 43.4
AE leading to discontinuation
25.4 14.0
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Tournigand C, et al. ASCO GI 2013. Abstract 457.
� Primary endpoint: PFS
� Secondary endpoints: duration of disease control, OS, ORR, chemotherapy-free interval, salvage surgery rates, safety, QoL, pharmacogenetics, pharmacoeconomics
� Patients stratified by ECOG PS, number of metastatic sites (1 vs > 1), age, previous adjuvant chemotherapy, and baseline alkaline phosphatase
Phase III DREAM Study: First-line Bev + Chemo ± Erlotinib in Unresectable mCRC
PD
PD
Patients with untreated,
unresectable mCRC,
ECOG PS ≤ 2 (N = 700)
R
Bev (n = 224)
Bev +Erlotinib (n = 222)
CR
PR
SD
CAPOX + Bev (n = 204)
FOLFOX + Bev (n = 429)
FOLFIRI + Bev (n = 67)
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Tournigand C, et al. ASCO GI 2013. Abstract 457.
DREAM Study of First-line Bev + Chemo ±Erlotinib in Unresectable mCRC: PFS� Conclusion: Induction therapy for mCRC using modified biweekly
CAPOX + Bev provides similar response rates and PFS as mFOLFOX7 + Bev and FOLFIRI + Bev
Regimen n Median PFS HR (95% CI) P ValueFOLFIRI + Bev 67 9.0 mo 0.94 (0.69-1.29) .723mFOLFOX7 + Bev 429 8.6 mo 1.00mCAPOX + Bev 204 9.0 mo 0.99 (0.81-1.23) .964
Pat
ient
s w
ithou
t pr
ogre
ssio
n, %
Months
mCAPOX + BevmFOLFOX + Bev
100
80
60
40
20
00 3 6 9 15 21 2412 18
FOLFIRI + Bev
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Phase III Trial: Pegfilgrastim vs Placebo After First-line Chemo + Bev in Adv. CRC
� Primary objective: incidence of grade 3/4 febrile neutropenia in cycles 1-4
� Secondary endpoints: ORR, PFS, OS
Pinter T, et al. ASCO GI 2013. Abstract LBA445.
Patients with unresectable, locally
advanced or metastatic CRC who
received first-line FOLFOX or FOLFIRI
+ bevacizumab(N = 845)
Pegfilgrastim 6 mg ~ 24 hrsafter chemotherapy q2w x 4 cycles
(n = 422)
Placebo(n = 423)
Option to continue treatment until
progression
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Pegfilgrastim vs Placebo After First-line Chemo + Bev in Adv. CRC: Results� Pegfilgrastim significantly reduced the incidence of grade 3/4 febrile
neutropenia in patients receiving standard chemotherapy + Bev for CRC
Pinter T, et al. ASCO GI 2013. Abstract LBA445.
Result, % Placebo (n = 423)Pegfilgrastim
(n = 422)Placebo vs
Pegfilgrastim
Grade 3/4 FN (95% CI) 5.7 (3.7-8.3) 2.4 (1.1-4.3)Diff = -3.3% (-6.6 to 0)OR: 0.41 (0.19-0.86)
P = .014
ORR* (95% CI) 56.7† (51.8-61.5) 58.1† (53.2-62.0)Diff = 1.4% (-6.5 to 9.3)
OR: 1.06 (0.81-1.39)P = .683
Median PFS,* mos(95% CI)
10.1 (9.3-11.1) 9.7 (9.2-10.8)HR: 1.05 (0.88-1.26)
P = .552
Median OS,* mos(95% CI)
24.6 (21.3-NR) 21.8 (18.5-25.6)HR: 1.05 (0.81-1.36)
P = .704
*Immature data. †Measurable disease.
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Phase II PEAK Trial: First-line mFOLFOX6 + Panitumumab or Bevacizumab in mCRC
� Primary objective: PFS
� Secondary endpoints: OS, ORR, safety, resection rate, biomarker analysis (exploratory)
Schwartzberg LS, et al. ASCO GI 2013. Abstract 446.
Patients with untreated mCRC,
ECOG PS 0-1, and wild-type KRAS
(N = 285)
Panitumumab 6.0 mg/kg q2w +mFOLFOX6 q2w
(n = 142)
Bevacizumab 5.0 mg/kg q2w +mFOLFOX6 q2w
(n = 143)
Treatment until PD, death, or study
withdrawal
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Phase II PEAK Trial of First-line mFOLFOX6 + Panit or Bev in mCRC: PFS
� PFS similar between arms
� ORR similar between arms: 58% for panitumumab vs 76% for bevacizumab
Schwartzberg LS, et al. ASCO GI 2013. Abstract 446.
Eve
nt-F
ree
Sur
viva
l (%
)
Mos
Bev + mFOLFOX6
Panit + mFOLFOX6100
80
60
40
20
0
90
70
50
30
10
0 4 8 12 20 28 3416 24 322 6 10 18 2614 22 30
Panit + mFOLFOX6, n = 90/142 (63%)Median PFS: 10.9 mos (95% CI: 9.4-13.0)
Bev + mFOLFOX6, n = 94/143 (66%)Median PFS: 10.1 mos (95% CI: 9.0-12.6)
HR: 0.87 (95% CI: 0.65-1.17; P = .35)
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CORRECT Trial Analysis: Biomarkers and Response to Regorafenib in mCRC� Mutational analysis of biomarker samples in phase III
CORRECT study, which compared regorafenib vs placebo in patients with progressive mCRC
� Genes and mutations analyzed at study entry (fresh plasma samples or tumor tissue)
– KRAS (G12A, C, D, R, S, V; G13D; Q61H; A146T)
– PIK3CA (E542K; E545G, K; H1047L, R, Y)
– BRAF (V600E)
Jeffers M, et al. ASCO GI 2013. Abstract 381.
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Biomarkers and Response to Regorafenib in mCRC: OS and PFS in CORRECT Trial
Jeffers M, et al. ASCO GI 2013. Abstract 381.
PF
S
� Regorafenib showed a trend for clinical benefit vs placebo in all subgroups analyzed
� However, these data suggest that neither KRAS or PIK3CAmutational status is a useful biomarker to select patients most likely to benefit from regorafenib
KRAS-WT (plasma)KRAS-MU (plasma)
KRAS-WT (tumor)KRAS-MU (tumor)
PIK3CA-WT (plasma)PIK3CA-MU (plasma)
PIK3CA-WT (tumor)PIK3CA-MU (tumor)
KRAS-MU + PIK3CA-MU (plasma)KRAS-MU + PIK3CA-WT (plasma)KRAS-WT + PIK3CA-WT (plasma)
Overall study population
KRAS-WT (plasma)KRAS-MU (plasma)
KRAS-WT (tumor)KRAS-MU (tumor)
PIK3CA-WT (plasma)PIK3CA-MU (plasma)
PIK3CA-WT (tumor)PIK3CA-MU (tumor)
KRAS-MU + PIK3CA-MU (plasma)KRAS-MU + PIK3CA-WT (plasma)KRAS-WT + PIK3CA-WT (plasma)
Overall study population
n = 154 (71)n = 349 (205)n = 99 (55)n = 140 (82)n = 419 (224)n = 84 (52)n = 207 (123)n = 29 (15)n = 67 (40)n = 282 (165)n = 137 (59)n = 760 (432)
n = 154 (130)n = 349 (311)n = 99 (82)n = 140 (128)n = 419 (366)n = 84 (75)n = 207 (180)n = 29 (26)n = 67 (60)n = 282 (251)n = 137 (115)n = 760 (671)
10.250.33 0.50.67 1.5 2 3 4 5 60.170.2
HR (Regorafenib/Placebo)10.25 0.33 0.5 0.67 1.5 2 3 4
OS
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Stage II Colon Cancer: Adding Recurrence Score and MMR Status to Risk Assessment� In stage II colon cancer, risk assessment based on
traditional clinicopathologic factors and varies widely
� Survey conducted to compare level of physician agreement using traditional factors alone or with addition of recurrence score (Oncotype DX) and MMR status
– Data source: 20 patients with stage II colon cancer enrolled on 2 CALGB studies
– Conventional clinicopathologic data included T-stage, grade, LVI status, perforation/obstruction status, location, number of nodes
– Participants: university- and community-based oncologists
Kelley RK, et al. ASCO GI 2013. Abstract 349.
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CP CP+
Community Based
AS
D
250
200
150
100
50
0
CP CP+
University Based
AS
D
250
200
150
100
50
0
Recurrence Score and MMR Status in Risk Assessment in Colon Cancer: Results� Addition of recurrence
score result and MMR to conventional clinicopathologic criteria significantly improved agreement and decreased variability in risk assessment of stage II colon cancer
� Agreement in risk estimates higher among community vs university physicians
Kelley RK, et al. ASCO GI 2013. Abstract 349.
Esophageal and Stomach Cancer
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Phase III COUGAR -02 Trial: Docetaxel vs ASC in Esophagogastric Cancer
� Primary objective: OS
� Secondary endpoints: response to docetaxel, TTP, QoL, toxicity
Ford H, et al. ASCO GI 2013. Abstract LBA4.
Patients with locally advanced or
metastatic OGC, PS 0-2, progression
within 6 mos of chemotherapy
(N = 168)
Docetaxel 74 mg/m2 IV q3w +Active Symptom Control
(n = 84)
Active Symptom Control(n = 84)
Assess q3w for 18 wks, then q6w
Stratified by disease status (LA vs advanced), site (esophagus vs GEJ vs stomach), TTP (0 vs 0-3 vs 3-6 mos,
ECOG PS (0-1 vs 2)
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COUGAR-02 Trial of Docetaxel vs ASC in Esophagogastric Cancer: OS
Ford H, et al. ASCO GI 2013. Abstract LBA4.
Pat
ient
s R
emai
ning
Aliv
e (%
)
Mos From Randomization
ASC
Docetaxel
Pts at Risk, nDocetaxel 84 69 53 33 25 17 10 8 5 4ASC 84 70 38 19 13 9 6 2 1 1
100
50
0
75
25
0 2 4 6 10 14 188 12 16
Median Survival, Mos (95% CI)Docetaxel: 5.2 (4.1-5.9)ASC: 3.6 (3.3-4.4)
HR: 0.67 (95% CI: 0.49-0.92; P = .01)
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COUGAR-02 Trial of Docetaxel vs ASC in Esophagogastric Cancer: Grade 3/4 AEs
AEDocetaxel ASC
n % n %Allergy 2 3 0 0Blood/bone marrow 18 22 6 8� Neutropenia 14 18 0 0� Anemia 5 6 5 7� Thrombocytopenia 2 3 0 0
Constitutional symptoms 13 16 10 14Gastrointestinal 21 26 18 24Infection 15 19 2 3Febrile neutropenia 6 7 0 0Neuropathy 3 4 3 4Hemorrhage/bleeding 1 1 5 7Pain 9 11 15 20
Ford H, et al. ASCO GI 2013. Abstract LBA4.
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Phase III REGARD Trial: BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer
� Primary objective: OS
� Secondary endpoints: PFS, 12-wk PFS, ORR, DOR, QoL, safety
Fuchs CS, et al. ASCO GI 2013. Abstract LBA5.
Patients with metastatic gastric or GEJ
adenocarcinoma progressing on first-line
platinum- and/or fluoropyrimidine-
containing combination therapy, ECOG PS 0-1
(N = 355)
Ramucirumab 8 mg/kg IV q2w +BSC
(n = 238)
BSC + Placebo(n = 117)
Treatment until PD, unacceptable
toxicity, or death
Stratified by geographic region, weight loss (> vs < 10% over 3 mos), location of primary tumor (gastric vs GEJ)
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REGARD Trial of BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer: OS
Fuchs CS, et al. ASCO GI 2013. Abstract LBA5.
Pts at Risk, nRamucirumabPlacebo
Pro
ortio
n re
mai
ning
aliv
e
Mos
Ramucirumab Placebo Patients/events 238/179 117/99Median, mos 5.2 (4.4-5.7) 3.8 (2.8-4.7)(95% CI)
6-mo OS, % 42 3212-mo OS, % 18 11
HR: 0.776 (95% CI: 0.603-0.998; P = .0473).
1.0
0.8
0.6
0.4
0.2
00 2 4 6 10 14 208 12 171 3 5 7 11 15 169 13 18 19 26 2827
238117
15466
9234
4920
177
74
32
01
00
RamucirumabPlaceboCensored
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REGARD Trial of BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer: PFS
Fuchs CS, et al. ASCO GI 2013. Abstract LBA5.
Pro
port
ion
with
out
prog
ress
ion
RamucirumabPlaceboCensored
Ramucirumab PlaceboPatients/events 238/199 117/108Median, mos 2.1 (1.5-2.7) 1.3 (1.3-1.4)(95% CI)
12-wk PFS, % 40 16
HR: 0.483 (95% CI: 0.376-0.620; P < .0001)
1.0
0.8
0.6
0.4
0.2
00 2 4 6 10 148 12 171 3 5 7 11 15 169 13
Mos
238117
21392
11327
6511
112
52
21
10
00
10
10
10
41
182
617
454
302
182
Pts at Risk, nRamucirumabPlacebo
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REGARD Trial of BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer: AEs
Ramucirumab (n = 236) Placebo (n = 115)
Treatment-Emergent AE, % Any Grade Grade ≥ 3 Any Grade Grade ≥ 3
Fatigue* 35.6 6.4 40.0 9.6
Abdominal pain* 28.8 5.9 27.8 2.6
Decreased appetite 24.2 3.4 22.6 3.5
Vomiting 19.9 2.5 25.2 4.3
Hypertension*† 16.1 7.6 7.8 2.6
Constipation 15.3 0.4 22.6 2.6
Anemia* 14.8 6.4 14.8 7.8
Dysphagia 10.6 2.1 10.4 4.3
Ascites 9.7 4.2 9.6 4.3
Dyspnea 9.3 1.7 13.0 6.1
Back pain 7.6 1.3 9.6 2.6
Fuchs CS, et al. ASCO GI 2013. Abstract LBA5.
*Consolidated terms: fatigue includes asthenia; abdominal pain includes abdominal pain upper; hypertension includes elevated blood pressure; anemia includes hematocrit decreased and red blood cell decreased.†No grade 4 hypertension observed among ramucirumab-treated patients.
Pancreatic Cancer
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Phase II SCALOP Trial: Gem - or Cape -Based CRT in Locally Advanced Pancreatic Cancer
� Clinical, Ca19.9, and CT assessments at Weeks 26, 39, and 52
� Primary objective: 9-mo PFS
Mukherjee S, et al. ASCO GI 2013. Abstract LBA146.
Patients with inoperable,
locally advanced prostate cancer < 7 cm diameter,
WHO PS 0-2(N = 74)
Gem 300 mg/m2/wk IV +Radiation* 50.4 Gy in 28 fractions
(n = 36)
Cape 830 mg/m2/day PO M-F +Radiation * 50.4 Gy in 28 fractions
(n = 38)
Assess for operability
GEMCAP x 4 cyclesGem 1000 mg/m2
on Days 1, 8, 15 q4w +Cape 830 mg/m2
on Days 1-21 q4w
*3D conformal or IMRT
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SCALOP Trial of Gem - or Cape -Based CRT in Locally Advanced Pancreatic Cancer: PFS
Mukherjee S, et al. ASCO GI 2013. Abstract LBA146.
Gem CRT (n = 38)Cape CRT (n = 36)
HR: 0.60(95% CI 0.32-1.12;P = .111)
Pro
port
ion
With
PF
S
Mos From RegistrationPts at Risk, nCape CRT 36 33 17 4 0 0Gem CRT 38 37 12 0 0 0
Median PFSCape: 12Gem: 10.4
Median Distant PFS, MosCape: 14.3Gem: 11.9
Median Local PFS, MosCape: 14.6Gem: 12.0
0 6 12 18 3024
1.00
0.25
0
0.75
0.50
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SCALOP Trial of Gem - or Cape -Based CRT in Locally Advanced Pancreatic Cancer: OS
Mukherjee S, et al. ASCO GI 2013. Abstract LBA146.
Pts at Risk, nCapecitabine CRT 36 35 24 7 1 0Gemcitabine CRT 38 37 20 2 0 0
Cape + RT median OS: 15.2 mos(95% CI: 13.9-19.2)1-yr OS: 79.2%(95% CI: 61.1-89.5)
Gem + RT median OS: 13.4 mos(95% CI: 11.0-15.7)1-yr OS: 64.2%(95% CI: 46.4-77.5)
HR: 0.39(95% CI: 0.17-0.81;P = .012)
Gem CRTCape CRT
Pro
port
ion
With
OS
0 6 12 18 3024
1.00
0.25
0
0.75
0.50
Mos From Registration
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SCALOP Trial of Gem - or Cape -Based CRT in Locally Advanced Pancreatic Cancer: AEs
Capecitabine (n = 36) Gemcitabine (n = 38)P Value
Grade 3/4 Adverse Event n % n %
Any CTCAE grade 3/4 4 11.1 14 36.8
Hematologic 0 0 7 18.4 .007
� Febrile neutropenia 0 0 1 2.6
Nonhematologic 4 11.1 10 26.3 .095
� Fatigue 2 5.6 4 10.5
� Weight loss 0 0 1 2.6
� Diarrhea 0 0 3 7.9
� Stomatitis 0 0 0 0
� Nausea/vomiting 0 0 3 7.9
� Anorexia 0 0 3 7.0
� GI bleeding 0 0 0 0
Mukherjee S, et al. ASCO GI 2013. Abstract LBA146.
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Phase III MPACT Trial: Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer
� Primary objective: OS
� Secondary endpoints: PFS, ORR, safety
Von Hoff DD, et al. ASCO GI 2013. Abstract LBA148.
Patients with metastatic pancreatic cancer, no previous
treatment for metastatic disease, KPS ≥ 70, bilirubin
≤ ULN(N = 861)
nab-Paclitaxel 125 mg/m2 IV q3w +Gemcitabine 1000 mg/m2
on Days 1, 8, 15 q4w(n = 431)
Gemcitabine 1000 mg/m2/wk for 7 wks, then on Days 1, 8, 15 q4w
(n = 430)
Treat until PD
Stratified by KPS, region, liver metastasis
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MPACT Trial of Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer: OS
Von Hoff DD, et al. ASCO GI 2013. Abstract LBA148.
1.00.90.80.71.60.50.40.30.20.1
00 3 6 9 12 15 18 21 24 27 30 33 36 39
Mos
Pro
port
ion
of S
urvi
ving
Pat
ient
s nab-P + GemOS, Mos
Events,n/N (%)
Median (95% CI)
75thPercentile
333/431 (77) 8.5 (7.89-9.53) 14.8
359/430 (83) 6.7 (6.01-7.23) 11.4
Gem
HR: 0.72(95% CI: 0.617-0.835;P = .000015)
431430
357340
269220
169124
10869
6740
4026
2715
167
93
41
10
10
00
Pts at Risk, nnab-P + GemGem
clinicaloptions.com/oncologyGastrointestinal Cancers
MPACT Trial of Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer: PFS
Von Hoff DD, et al. ASCO GI 2013. Abstract LBA148.
1.00.90.80.71.60.50.40.30.20.1
00 3 6 9 12 15 18 21 24
Mos
Pro
port
ion
of
Pat
ient
s W
ithou
t Pro
gres
sion
Pts at Risk, nnab-P + GemGem
431430
281209
12251
6223
2410
86
44
20
00
PFS, Mos
Events, n/N (%)
Median (95% CI)
75thPercentile
277/431 (64) 5.5 (4.47-5.95) 9.2
265/430 (62) 3.7 (3.61-4.04) 5.9
HR: 0.6995% CI (0.581-0.821;P = .000024)
PFS Rate at6 mos
12 mos
nab-P + Gem44%16%
Gem25%9%
% Increase76%78%
nab-P + GemGem
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MPACT Trial of Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer: AEsAdverse Event nab-P + Gem (n = 421) Gem (n = 402)≥ 1 AE leading to death, % 4 4Grade ≥ 3 hematologic AE,* %� Neutropenia 38 27� Leukopenia 31 16� Thrombocytopenia 13 9� Anemia 13 12
Receipt of growth factors % 26 15Febrile neutropenia†, % 3 1Grade ≥ 3 nonhematologic AE† in > 5% pts, %� Fatigue 17 7� Peripheral neuropathy 17 < 1� Diarrhea 6 1
Grade ≥ 3 neuropathy� Time to onset, median days 140 113� Time to improvement by grade, median days 21 29� Time to improvement to grade ≤ 1, median days 29 --� Resumed nab-P, % 44 --
Von Hoff DD, et al. ASCO GI 2013. Abstract LBA148.*Based on lab values. †Based on investigator assessment of treatment-related events.
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MPACT Trial of Gem ± nab-Paclitaxel in Metastatic Pancreatic Cancer: Conclusions� Addition of nab-paclitaxel to gemcitabine improves survival
– Across entire curve at all time points
– Median OS: 8.5 vs 6.7 mos with gemcitabine alone (HR: 0.72; P = .000015)
– 1-yr OS: 59% increase
– 2-yr OS: 9% vs 4%
� Significant improvement in PFS, ORR, and all other efficacy endpoints with consistent improvement across subgroups
� Serious AEs not increased, remain acceptable and manageable
� Nab-paclitaxel plus gemcitabine potentially a new standard for the treatment of metastatic pancreatic cancer
– Could become backbone of new regimensVon Hoff DD, et al. ASCO GI 2013. Abstract LBA148.
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Phase III JASPAC -01 Trial: Adjuvant Gem vs S-1 in Resected Pancreatic Cancer
� Primary endpoint: OS
� Secondary endpoints: RFS, safety, quality of life
Uesaka K, et al. ASCO GI 2013. Abstract 145.
Patients with curatively resected pancreatic cancer (stage I-III), ECOG PS 0-1, no previous
chemo or RT(N = 378)
Gemcitabine 1000 mg/m2
on Days 1, 8, 15, q4w6 courses (n = 191)
S-1 40-60 mg BID for 4 of 6 wks 4 courses (n = 187)
Stratified by institution, residual tumor status (R0 vs R1), nodal status (N0 vs N1)
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JASPAC -01 Trial of Adjuvant Gem vs S -1 in Resected Pancreatic Cancer: OS
Uesaka K, et al. ASCO GI 2013. Abstract 145.
HR of S-1: 0.56(99.8% CI: 0.36-0.87;P < .0001 for noninferiority;P < .0001 for superiority, log-rank test)
Pts at Risk, nS-1 187 172 127 68 28 1Gem 191 151 95 51 16 3
Pat
ient
s re
mai
ning
aliv
e, %
Yrs
Gem: 123 pts (64%) died
S-1: 82 pts (44%) died100
0
50
0 1 2 3 54
2-yr OS70% (95% CI: 63-76)
2-yr OS53% (95% CI: 46-60)Median OS: 25.5 mos
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JASPAC -01 Trial of Adjuvant Gem vs S -1 in Resected Pancreatic Cancer: AEs
Uesaka K, et al. ASCO GI 2013. Abstract 145.
Laboratory Data, %Gem (n = 191) S-1 (n = 187)
Grade 3 Grade 4 Grade 3 Grade 4Leukocytes 32 7 4 5Hemoglobin 9 8 9 5Platelets 2 7 0 4Bilirubin 0 0.5 1 0AST 5 0 1 0ALT 4 0 0.5 0Creatinine 0 0.5 0.5 0
Symptom, %Gem (n = 191) S-1 (n = 187)
Grade 3 Grade 4 Grade 3 Grade 4Stomatitis 0 0 3 0Anorexia 5 0.5 8 0Nausea 2 1 4 0Vomiting 0.5 0.5 2 0Diarrhea 0 0 4 0.5Fatigue 5 0 5 0.5Fever 0.5 0 3 0Febrile neutropenia 2 0 0.5 0
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Prospective Phase II Trial: GTX in Patients With Metastatic Pancreatic Cancer� Gemcitabine/docetaxel/capecitabine (GTX) regimen
– Decreases Bcl-2 and -XL expression
– Increases intracellular gemcitabine accumulation
– Inhibits MEK to ERK phosphorylation
� Phase II study (N = 44) in untreated metastatic pancreatic cancer
– Treatment: capecitabine 750 mg/m2 BID, on Days 1-14; gemcitabine 750 mg/m2 on Days 4, 11; docetaxel 30 mg/m2
on Days 4, 11
– > 85% with liver metastasesFine R, et al. ASCO GI 2013. Abstract 209.
clinicaloptions.com/oncologyGastrointestinal Cancers
GTX in Patients With Metastatic Pancreatic Cancer: Results� Responses
– ORR: 38%
– CR: 9%
– SD: 38%
� Median PFS: 6.9 mos
� Median OS: 14.5 mos
� Grade 3/4 toxicities: leucopenia, infection, neutropenia, thrombocytopenia
Fine R, et al. ASCO GI 2013. Abstract 209.
Pat
ient
s re
mai
ning
aliv
e, %
100
80
60
40
20
0
90
70
50
30
10
0 12 24 36 486 18 30 42
Mos
14.5 mos
Survival (n = 42)Mo % 6 75.612 58.518 34.124 14.636 4.9
clinicaloptions.com/oncologyGastrointestinal Cancers
pCR, nCR Rates After Chemo + SBRT in Borderline Resectable Pancreatic Cancer� Single-institution, retrospective review of 35 patients with
BRPC who completed gemcitabine-based induction therapy and 5-fraction SBRT prior to resection
� Each specimen assigned 2 tumor regression grade scores (CAP and MDACC)
� Neoadjuvant treatment with a gemcitabine-based regimen plus SBRT shown to produce
– Significant pathologic response
– Potential OS and PFS benefit (both P = .019), based on MDACC response
Chuong M, et al. ASCO GI 2013. Abstract 221.
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