CCO_Clin_Onc_2016_GI_LBA4006_Neoptolemos_Slides.ppt

CANCER DE PANCREAS ADYUVANCIA ESPAC-4

1. CCO Independent Conference Coverage*
of the 2016 ASCO Annual Meeting, June 3-7, 2016
ESPAC-4: Adjuvant Gemcitabine/
Capecitabine Improves 5-Yr Survival
vs Gemcitabine Alone in Resected
Pancreatic Ductal Carcinoma
*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.
This activity is supported by educational grants from Amgen, Ariad,
Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech,
Incyte, Merck, and Taiho Pharmaceuticals.

2. Adjuvant Gemcitabine/Capecitabine in
Pancreatic Cancer: Background
ESPAC-1 (N = 289): CRT not superior to no CRT (HR: 1.28;
P= .053) for resected pancreatic ductal adenocarcinoma but
chemotherapy superior to no chemotherapy (HR: 0.71;
P= .009)
[1,2]
ESPAC-3 (N = 1088): gemcitabine not superior to 5-FU/
leucovorin
–Median OS: nearly 24 mos in both arms
[3]
Current multicenter, international, open-label, randomized,
controlled phase III trial, ESPAC-4, evaluated adjuvant
gemcitabine + capecitabine vs gemcitabine in pts pancreatic
ductal adenocarcinoma undergoing intended curative
resection
[4]
1. Neoptolemos JP, et al. Lancet. 2001;358:1576-1585. 2. Neoptolemos JP, et al.
Lancet. 2004;350:1200-1210. 3. Neoptolemos JP, et al. JAMA. 2010;304:
1073-1081. 4. Neoptolemos JP, et al. ASCO 2016. Abstract LBA4006.Slide credit: clinicaloptions.com

3. Phase III ESPAC-4: Adjuvant GEMCAP vs
GEM in Resected Pancreatic Cancer
Primary endpoint: OS
Secondary endpoint: toxicity, RFS, 2-and 5-yr
survival, and QoL
Pts with pancreatic ductal
adenocarcinoma
undergoing macroscopic
R0 or R1 (≤ 1 mm any
surface) resection, WHO
PS ≤ 2, no prior or
concurrent malignancies,
life-expectancy > 3 mos
(N = 730)
Follow-up every
3 mos from
randomization
until death
Gemcitabine 1000 mg/m
2
Days 1, 8, 15 for 6 cycles +
Capecitabine 1660 mg/m
2
/day
21/28 days
(n = 364)
Gemcitabine 1000 mg/m
2
Days 1, 8, 15 for 6 cycles
(n = 366)
Slide credit: clinicaloptions.comNeoptolemos JP, et al. ASCO 2016. Abstract LBA4006.

4. Slide credit: clinicaloptions.com
ESPAC-4: Baseline Characteristics
Trial was stopped early byIndependent Trial Steering Committee due to efficacy
Median follow-up of alive patients: 43.2 mos (95% CI: 39.7-45.5)
Characteristic GEMCAP
(n = 364)
GEM
(n = 366)
Total
(N = 730)
Median age, yrs (range) 65 (39-81) 65 (37-80) 65 (37-81)
Male, % 55 58 57
Baseline PS, %
0
1
2
41
56
3
43
54
3
42
55
3
Smoking status, %
Never
Past
Present
Unknown
40
41
17
2
41
37
17
5
41
39
17
3
Surgery to randomization, median
days (range)
64 (21-111) 65 (23-111)
64 (21-111)
Neoptolemos JP, et al. ASCO 2016. Abstract LBA4006.

5. No difference in treatment-related serious AEs between treatment arms
−24% with GEMCAP vs 26% with gemcitabine; Χ
2
df1 test P >.05
ESPAC-4: Toxicity
Slide credit: clinicaloptions.comNeoptolemos JP, et al. ASCO 2016. Abstract LBA4006.
*Exploratory analysis: Fisher’s exact test
Grade 3/4 AE (NCI CTC v4), % GEMCAP
(n = 359)
GEM
(n = 366)
P Value*
Anemia 2 4 .279
Diarrhea 5 2 .008
Fatigue 6 5 .870
Fever 2 2 1.000
Infection and infestations, other 3 7 .012
Lymphocytes 3 3 .821
Neutrophils 38 24 < .001
Hand-foot syndrome 7 0 < .001
Platelets 2 2 .800
Thromboembolic event 2 2 1.000
WBC 10 8 .242

6. ESPAC-4: Survival
Greatest benefit with GEMCAP and R0, but treatment benefit evident even
with R1 resection
Slide credit: clinicaloptions.com
Neoptolemos JP, et al. ASCO 2016. Abstract LBA4006.
Reproduced with permission.
100
90
80
70
60
50
40
30
20
10
0
OS (%)
Mos From Randomization
600 10 20 30 40 50
Gemcitabine
Gemcitabine-Capecitabine
HR: 0.82 (95% CI: 0.68-0.98)
χ
2
(1): 4.61; P= .032
Median S(t): 25.5 mos(95%CI: 22.7-27.9)
Median S(t): 28.0 mos(95% CI: 23.5-31.5)
Pts at Risk, n
GEM
GEMCAP
366
364
9
19
302
328
207
219
109
139
61
83
27
50

7. ESPAC-4: Factors Affecting OS
Slide credit: clinicaloptions.comNeoptolemos JP, et al. ASCO 2016. Abstract LBA4006.
Reproduced with permission.
Mos From Randomization
OS (%)
100
90
80
70
60
50
40
30
20
10
0
0 10 20 30 40 50 60
Well
Moderate
Poor
Survival by Grade of Disease
χ
2
(2): 38.21; P< .001
Median S(t): 41.1
Median S(t): 30.7
Median S(t): 19.0
Mos From Randomization
OS (%)
100
90
80
70
60
50
40
30
20
10
0
0 10 20 30 40 50 60
I
II
III
IV
Survival by Stage of Disease
χ
2
(3): 12.71; P= .005
Mos From Randomization
OS (%)
100
90
80
70
60
50
40
30
20
10
0
0 10 20 30 40 50 60
Negative
Positive
Survival by Lymph Nodes
χ
2
(1): 38.66; P< .001
Median S(t): 58.0
Median S(t): 23.5
Mos From Randomization
OS (%)
100
90
80
70
60
50
40
30
20
10
0
0 10 20 30 40 50 60
R0
R1
Survival by Resection Margins
χ
2
(1): 17.65; P< .001
Median S(t): 34.6
Median S(t): 23.3
Median S(t): N/A
Median S(t): 39.3
Median S(t): 26.0
Median S(t): 15.7

8. Adjuvant GEMCAP vs GEM in Pancreatic
Cancer: 5-Year OS in ESPAC Studies
Trial Treatment Pts, n
(N= 2092)
5-YrOS, %
(95% CI)
Stratified
Log-Rank
Χ
2
P Value
ESPAC-1 5-FU/
leucovorin
149 21
(14.6-28.5)
7.03 .030*
No
chemotherapy
143 8.0 (3.8-14.1)
CRT
(5-FU/RT)
145 10.8 (6.1-17.0)
ESPAC-3 GEM 539 17.5 (14.0-21.2)
0.74 .390*
5-FU/
leucovorin
551 15.9 (12.7-19.4)
ESPAC-4 GEM 366 16.3 (10.2-23.7) 4.61 .032
†
GEMCAP 364 28.8 (22.9-35.2)
Slide credit: clinicaloptions.comNeoptolemos JP, et al. ASCO 2016. Abstract LBA4006.
*Stratification factor: resection margin status.
†
Stratification factors: resection margin status and country.

9. ESPAC-4: Conclusions
Median survival for pts with resected pancreatic cancer who received
GEMCAP was significantly longer than with GEM
–28.0 vs 25.5 mos, respectively
Estimated 5-yr survival with GEMCAP superior vs GEM: 28.8 vs
16.3 mos, and superior to previous ESPAC trial arms, including 5-
FU/leucovorin, CRT, and no chemotherapy
Higher toxicity in GEMCAP arm manageable, not significant: 154
serious AEs in 86 pts treated with GEMCAP (24%) vs 151 serious AEs
in 94 pts with GEM (26%)
Investigators recommend offering all pts with pancreatic cancer the
opportunity to participate in trials
–Evaluation of relevant biomarkers needed
Investigators suggest that GEMCAP is the new standard of care for
resected pancreatic cancer
Slide credit: clinicaloptions.comNeoptolemos JP, et al. ASCO 2016. Abstract LBA4006.

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