Cco Gi Cr 2013 Slides

January 24-26, 2013San Francisco, California

Gastrointestinal CancersCCO Independent Conference Coverageof the 2013 Gastrointestinal Cancers Symposium*

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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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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


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.


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


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


TRIBE Trial of First-line Bev + FOLFIRI or FOLFOXIRI in mCRC: PFS


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


TRIBE Trial of First-line Bev + FOLFIRI or FOLFOXIRI in mCRC: Response Rates


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


TRIBE Trial of First-line Bev + FOLFIRI or FOLFOXIRI in mCRC: Safety


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


Phase III AVEX Trial: First-line Capecitabine ± Bev in Elderly mCRC Pts


� 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


AVEX Trial of First-line Capecitabine ± Bev in Elderly mCRC Pts: PFS


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


AVEX Trial of First-line Capecitabine ± Bev in Elderly mCRC Pts: ORR and AEs


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


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)


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


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


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.


Phase II PEAK Trial: First-line mFOLFOX6 + Panitumumab or Bevacizumab in mCRC


� 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


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)


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.


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


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.


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


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)


COUGAR-02 Trial of Docetaxel vs ASC in Esophagogastric Cancer: OS


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)


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



Phase III REGARD Trial: BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer


� 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)


REGARD Trial of BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer: OS


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


REGARD Trial of BSC ± Ramucirumab in Metastatic Gastric or GEJ Cancer: PFS


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


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


*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


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


SCALOP Trial of Gem - or Cape -Based CRT in Locally Advanced Pancreatic Cancer: PFS


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


SCALOP Trial of Gem - or Cape -Based CRT in Locally Advanced Pancreatic Cancer: OS


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


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



Phase III MPACT Trial: Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer


� 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


MPACT Trial of Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer: OS


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


MPACT Trial of Gemcitabine ± nab-Paclitaxel in Metastatic Pancreatic Cancer: PFS


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


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.


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.


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)


JASPAC -01 Trial of Adjuvant Gem vs S -1 in Resected Pancreatic Cancer: OS


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


JASPAC -01 Trial of Adjuvant Gem vs S -1 in Resected Pancreatic Cancer: AEs


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


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.


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


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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