Annual Meeting Proceedings Part 1 - American Society of Clinical ...

4035 General Poster Session (Board #40B), Mon, 8:00 AM-12:00 PM
Updated results of the GEST study: Randomized phase III study of
gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in
unresectable advanced pancreatic cancer in Japan and Taiwan. Presenting
Author: Akira Fukutomi, Shizuoka Cancer Center, Sunto-gun, Japan
Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007)
demonstrated the non-inferiority of S-1 to GEM with respect to the primary
endpoint of overall survival (OS) in patients with pancreatic cancer (PC).
We now report the updated results of this study. Methods: The GEST study
was a randomized, 3-arm, phase III study. Chemotherapy-naive patients
with unresectable advanced PC, an ECOG Performance status (PS) of 0-1,
and adequate organ functions were randomly assigned to receive GEM
(1000 mg/m2 , iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on
BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2 , iv, d1 and 8 plus S-1
60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint
was OS, used to assess the non-inferiority of S-1 and the superiority of GS
to GEM. Patient information was updated in July 2011. Results: At the time
of this follow-up analysis, median follow-up was 29.8 months with 795 OS
events, compared with 18.4 months with 710 OS events out of 832
patients at the previous analysis. Median OS was 8.8 months (95% CI:
8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1
group (HR�0.96, 97.5% CI: 0.79-1.17, p�0.001 for non-inferiority),
which is consistent with prior results (HR�0.96, 97.5% CI: 0.78-1.18,
p�0.001). In the GS group, median OS was 9.9 months (95% CI:
9.0-11.2). The HR was 0.91 (97.5%CI: 0.75-1.11, p�0.28 for superiority
versus the GEM group). On subgroup analysis, GS was associated with a
non-statistically significant trend toward better OS compared with GEM
among patients with locally advanced disease and those with a PS of 1.
Median OS was 12.7 months (95% CI: 9.7–14.9) in the GEM group and
15.9 months (95% CI: 13.0-19.7) in the GS group (HR�0.72, 95% CI:
0.51-1.03) among patients with locally advanced disease, and 6.2 months
(95% CI: 4.9–8.3) in the GEM group and 9.6 months (95% CI: 8.0-10.9)
in the GS group (HR�0.62, 95% CI: 0.46-0.83) among patients with a PS
of 1. Conclusions: The non-inferiority of S-1 to Gem in terms of the primary
endpoint of OS was reconfirmed. Monotherapy with S-1 can be used as one
of the standard treatments for advanced PC. As for GS therapy, there is
room for further investigation.
4037 General Poster Session (Board #40D), Mon, 8:00 AM-12:00 PM
Incidence and characterization of venous thromboembolic events (VTE) in
patients with pancreatic cancer: Effect of timing of VTE on survival.
Presenting Author: Maithili A. Shethia, University of Texas M. D. Anderson
Cancer Center, Houston, TX
Background: Patients (pts) with pancreatic cancer are at high risk for VTE,
and the occurrence of VTE can affect pts’ prognosis. The purpose of this
study was to evaluate the incidence of VTE and the impact of timing of VTE
(early vs. late) on survival. Methods: Medical record of 260 pts with
pancreatic cancer, newly referred to UT MDACC during one year period
from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE
during a 2-year follow-up period from the date of diagnosis. All VTE
episodes were confirmed by radiologic studies. Survival analysis was
conducted using Kaplan-Meier analysis and Cox proportional hazard
models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE
during the 2-year follow-up. The median age of the pts with VTE was 61
years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27
(57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts
had recurrent VTE during the study period. Median follow-up time for OS
was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis
showed that those who developed VTE earlier (within 30 or 90 days) had
shorter median overall survival (OS) compared with those who had VTE
beyond these time points. The hazard ratios, 95% CI, and median OS at 1
year are summarized in the table below. Conclusions: The incidence of VTE
is high in pts with pancreatic cancer. The timing of VTE had a significant
impact on OS; pts who had an early development of VTE had a shorter
overall survival.
Timing of VTE*
1 year OS Median 1 year OS**
Hazard ratio
(95% CI) p value
Early VTE
vs. late VTE p value***
Within 30 days 3.52 (1.71-7.23) 0.0006 116 vs. 295 0.0003
Within 90 days 5.33 (1.85-15.35) 0.0019 152 vs. NR 0.0006
* From the date of diagnosis of pancreatic cancer to date of diagnosis of VTE; **
days; *** Log-rank; NR: not reached.
Gastrointestinal (Noncolorectal) Cancer
4036 General Poster Session (Board #40C), Mon, 8:00 AM-12:00 PM
Efficacy and safety of bevacizumab combined with chemotherapy in the
treatment of patients with metastatic well-differentiated duodenopancreatic
endocrine tumors (BETTER study). Presenting Author: Michel
Ducreux, Institut Gustave Roussy, Villejuif, France
Background: Gastrointestinal neuroendocrine tumors (NET) overexpress
vascular endothelial growth factor (VEGF), thus we hypothesized that
Bevacizumab (Bv), a monoclonal antibody targeting VEGF in combination
with chemotherapy may show an activity in duodeno-pancreatic NET.
Methods: This multicenter, open-label, non-randomized, two- group phase
II trial assessed in one group the efficacy and safety of Bv (7.5 mg/kg IV on
day 1, every 3 weeks), combined with 5-FU/streptozotocin (stz): 5-FU 400
mg/m²/d; Stz 500 mg/m²/d IV, d1-5/ every 42 days, during a minimum of 6
months in patients (pts) with progressive, metastatic, well-differentiated
duodeno-pancreatic NET (WHO 2000), not previously treated with chemotherapy,
ECOG PS �2 and Ki 67 index � 15%. Primary endpoint was
progression-free survival (PFS). Secondary endpoints were overall survival
(OS), response rate, safety and quality of life. Study duration was 24
months. Results: In the ITT population, 34 pts were enrolled, 22 (64.7%)
were men, median age 55.3 years (37.0-77.6), 33 (97.1%) pts had
ECOG-PS 0/1. Most metastases were in the liver 33 (97.1%) pts or lymph
nodes 14 (41.2%) pts. Ki-67 proliferative index was 0-2% in 8 (25%) pts,
3-4% in 5 (15.6%), 5-9% in 6 (18.8%), 10-14% in 12 (37.5%) and 15%
in 1(3.1%) pt. Median treatment duration was 14.0 months; median
number of cycles was 10. At 24 months, median PFS was 23.7 months
[95%CI: 14.5; not reached] based on 18 events. PFS rate at 18 months
was 62%. Tumor control rate was 100% (n� 34) including partial response
in 19 (55.9%) pts and stable disease in 15 (44.1%) pts. Survival rate at 24
months was 88%. Median OS was not reached, 5 patients died. CTC grade
3/4 Adverse Events (AEs) occurred in 23 (67.6%) of pts, mainly digestive 5
(14.7%) pts. G3/4 Bv targeted AEs were hypertension in 7 (20.6%) pts and
thromboembolism in 4 (11.8%). Conclusions: Efficacy data in this phase II
trial assessing a novel approach with Bv and 5-FU/stz in duodenopancreatic
NET is encouraging and the toxicity profile is acceptable.
Results suggest that Bv may have a place in the treatment of pancreatic
NET and warrant further investigation in a phase III trial.
4038 General Poster Session (Board #40E), Mon, 8:00 AM-12:00 PM
A pooled analysis of phase II trials of gemcitabine (GEM)-containing
doublets plus bevacizumab (BEV): Should combination chemotherapy
serve as the backbone in clinical trials of advanced pancreatic cancer
(APC)? Presenting Author: Katherine Van Loon, University of California,
San Francisco Comprehensive Cancer Center, San Francisco, CA
Background: GEM has served as the chemotherapy platform for most phase
III clinical trials in APC, inc. CALGB 80303 (GEM �/- BEV). However,
GEM-based combination regimens may confer superior outcomes in select
pts and represent a preferred backbone in clinical trial design testing
targeted agents. Methods: Data was pooled from 5 phase II trials evaluating
GEM-based cytotoxic doublets plus BEV in APC. 1 o endpoint was OS. 2o endpoints included ORR, CA19-9 response, and adverse events (AEs).
Kaplan-Meier methods estimated time-to-event endpoints. The Cox proportional
hazard model estimated univariate hazard ratios (HR) of death.
Results: Of 261 pts, 90.7% were Caucasian, 95.4% had an ECOG PS 0-1,
and 91.6% had metastatic disease. Median age � 60y. Pooled OS data (in
mos), stratified for PS and stage, is shown in the table. ORR across all
trials: CR 1.6%, PR 22.9%, SD 50.8%, PD 20.2%, NA 4.7%. HR for pts
who achieved disease control (CR/PR/SD) was 0.35 vs. those with PD (95%
CI 0.23-0.54, p�0.001). 76.5% of pts had elevated baseline CA19-9; of
these, 62% achieved �50% reduction (HR 0.50; 95% CI 0.34-0.73,
p�0.001). BEV-related AEs �grade 3: HTN (10.6%), hemorrhage (9.5%),
VTE (10.1%), cardiac events (3.4%), and bowel perforation (2.2%).
Median OS in pts with grade 3-4 HTN was 13.4 mos vs. 9.8 mos in those
without (HR 0.77; 95% CI 0.48-1.24, p�0.29). Conclusions: Recognizing
the limitations of single-arm phase II trial design and cross-study comparisons,
these results compare favorably to those from CALGB 80303. The
standard paradigm of GEM �/- drug X in clinical trial development for APC
needs to be reconsidered. Based on our data as well as the recent phase III
FOLFIRINOX study, building on more intensive combination chemo regimens
in future trials may represent a better strategy, especially for pts with
good PS.
gem/ox �
bev
gem/cap �
bev
gem/cis �
bev
gem/doc �
bev
gem/ox �
bev
Phase II
total
247s
CALGB
80303
N 50
Median OS 11.7
PS
0
1
2
Stage
Locally advanced
Metastatic
50
9.8
52
8.4
27
10.4
79
8.4
179†
9.9
11.1
9.1
3.3
14.2
9.5
602
5.8 - 5.9
7.9
4.8
2.4
9.9
5.7
† Reflects 4 studies with available raw data.
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