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

260s Gastrointestinal (Noncolorectal) Cancer
4087 General Poster Session (Board #46F), Mon, 8:00 AM-12:00 PM
Tolerability and efficacy of a biweekly docetaxel, fluorouracil, leucovorin,
oxaliplatin regimen (TFOX) in previously advanced metastatic gastric and
oesogastric junction (AGC) adenocarcinoma. Presenting Author: Simon
Pernot, Hôpital Européen Georges Pompidou, Paris, France
Background: The DCF regimen is superior to 5-FU-Cisplatin in term of
response rate (RR) and overall survival (OS) in advanced gastric cancer, but
is also more toxic. Oxaliplatin is better tolerated and can effectively replace
cisplatin in AGC patients (pts). We hypothesize that incorporating Docetaxel
into a simplified FOLFOX regimen should be a tolerable and
efficient option, and could facilitate the use of this drug in 1st line in AGC.
Methods: TFOX regimen was given biweekly as follow: Docetaxel (50mg/
m2), oxaliplatin (85mg/m2), leucoverin (400mg/m2) and 5FU continuous
infusion 48h (2400mg/m2). Main inclusion criteria were: pts with histollogically
proven metastatic or locally advanced gastric or oesogastric junction
adenocarcinoma, previously untreated, PS�2. Using Fleming design the
primary end point was response rate, needing a sample size of 40 pts.
Results: Between 02/2008 and 07/2011, 41 pts with AGC were enrolled
(oesogastric junction: 17 pts, diffuse type: 22 pts, metastatic: 37 pts);
mean age was 53.5 years (31-73), 26 pts were male. PS 0/1/2: 11/24/6
pts, 14 pts had a relapse after a R0 resection. The total number of cycles
administered was 310 (mean 7.6 cycles/pts) and 90% of pts received at
least 4 cycles. No toxic death occurred. Grade 3-4 toxicities were observed
in 20 pts (48%). Grade 3-4 toxicities were neutropenia (29%) febrile
neutropenia (7%), neurotoxicity (10%), asthenia (10%). ORR was 63%
(n�26) [IC95% 48-78], with 2 complete responses. Disease control rate
(CR�PR�SD) was 78% (n�32) [IC95% 65-90]. Median progression free
survival and overall survival were 6.5 months [IC95% 5.02-10.85] and
12.1 months [IC95% 7.25-15.28], respectively. Conclusions: TFOX is
effective with a manageable toxicity profile in first line treatment for AGC
pts. Tolerability of this regimen compares favourably with DCF reported
tolerability. TFOX may be an alternative option for intensive 1st line
treatment and should now be evaluated in randomized trials.
4089 General Poster Session (Board #46H), Mon, 8:00 AM-12:00 PM
Assessment of HER2 status from an epidemiology study in tumor tissue
samples of gastric and gastro-esophageal junction cancer: Spanish results
of the HER-EAGLE study. Presenting Author: Lourdes Gomez, Hospital
Virgen del Rocío, Sevilla, Spain
Background: Overexpression of HER2 is an important biomarker in gastroesophageal
junction (GEJ) and gastric cancer (GC) and a predictive factor
for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit
in overall survival of adding trastuzumab to chemotherapy inHER2-positive
advanced GEJ/GC patients, following validated scoring criteria by a central
laboratory. This study examines the incidence of HER2 positivity (local
laboratories) in GEJ/GC according to EMA Herceptin label. Methods:
HER-EAGLE was an epidemiological, non–interventional, international
study assessing HER2 status by IHC/ISH in tumor samples from any stage
GEJ/GC patients. Neutral buffered 10% formalin embedded tissues (surgical
excision specimens or minimum 6-8 biopsies) analyzed via validated
Ventana and Dako methods and scoring criteria used in ToGA: HER2positive
if IHC 3� or IHC 2� (FISH/SISH confirmed; HER2/CEP17 ratio �
2.0); HER2-negative if IHC 0 or IHC 1�. Overall and subgroup estimates
calculated with 95%CI. Data from the Spanish cohort are presented.
Results: The Spanish cohort of HER-EAGLE included 1,954 participants
(63.7% males) from 33 hospitals (Dec2010 to Aug2011), with 469
biopsies (24.0%) and 1,479 excisions (75.7%). Samples were 13.7% GEJ
and 86.3% GC, and the adenocarcinomas were 1,137 intestinal (58.2%),
510 diffused (26.1%), 163 mixed (8.3%; Laureen classification), and 144
not available (7.3%). Median time from sampling to HER2 analysis of 5.1
years (range from days to 12 years). Total of 210 cases tested IHC 3�
(10.7%), 215 IHC 2� (11.0%), 308 IHC 1� (15.8%), and 1,221 IHC 0
(62.5%). Overall, HER2 positivity (IHC 3� or IHC2�/ISH�) was 14.1%
(95%CI 12.61 – 15.75). HER2 positivity by histological type was higher in
intestinal adenocarcinomas (19.5%) compared to diffused (4.5%) or in
mixed (9.2%). Conclusions: HER-EAGLE confirmed the feasibility of
community based HER2 testing in GC as the first study with a high number
of samples analyzed by local laboratories. The incidence of HER2-positivity
(EMA label definition) was similar to the ToGA screening population, and it
was again higher in adenocarcinomas of intestinal type (19.5%).
4088 General Poster Session (Board #46G), Mon, 8:00 AM-12:00 PM
Prognostic value of lemur tyrosine kinase-3 (LMTK3) polymorphism in
Japanese (J) patients (PTS) with localized gastric adenocarcinoma (GAC).
Presenting Author: Afsaneh Barzi, Norris Comprehensive Cancer Center,
University of Southern California, Los Angeles, CA
Background: LMTK3 is an estrogen receptor � (ER�) regulator. Recent
studies show that [rs808419(r8) and rs9989661(r9)] and LMTK3 expression
are prognostic in breast and colon cancers. Our group demonstrated
that r9AA is associated with shorter time to recurrence in Caucasian(C) and
Hispanic(H) females(F) with GAC. We investigated the significance of
LMTK3 polymorphism in J PTS with GAC. Methods: Blood or tissue samples
of 169 J PTS who had surgery with/without adjuvant chemotherapy (ACT)
were analyzed. Genomic DNA was extracted using the QIAmp kit; all
samples were analyzed using PCR-based direct DNA-sequencing. The
endpoints of the study were disease-free survival (DFS) and overall survival
(OS). Kaplan-Meier curves and log-rank test were used for univariate
analysis. Multivariate analysis was performed to test the interaction
between polymorphism and gender adjusting for other variables. Results:
60 F and 109 males were enrolled in this study, 17% stage(s) IB, 31% s II,
36% s III, 17% s IV (AJCC-6). The median age was 67(31-88). 65% of PTS
received S-1 based ACT. Median follow-up was 4 years(ys). Prognosis was
worse in men with r9 AA than AG/GG, at 1 year 67% (95% CI 40-83%) with
AA vs 99% (95% CI 91-99%) of AG/GG were alive (p� 0.039). Median
survival was not reached in the AG/GG group; in the AA group median DFS
and OS was 1yr (p� 0.03) and 2ys (p� 0.039) respectively. In the
multivariate analysis adjusting for s, age, and ACT, males carrying AA had
increased risk of disease recurrence (HR 3.84 95%CI 1.86-7.92, p�
0.001) and dying (HR 3.47 95%CI 1.58-7.62 p�0.002) compared to
those with AG/GG (HR�1, reference). Conclusions: r9 AA was associated
with significantly worse DFS and OS in J male with GAC. These results
confirm our previous findings that LMTK3 is an independent prognostic
factor for localized GAC; interestingly the relationship between gender and
prognostic significance is the opposite in J vs. C/H. The gender disparity
can be due to the differences in the etiology (histological subtypes),
management strategies, allele frequency, and degree of estrogen exposure
in the two populations. Additional studies are warranted to identify the
underlying biological mechanism.
4090 General Poster Session (Board #47A), Mon, 8:00 AM-12:00 PM
A prospective trial for defining a subset of patients with limited metastatic
gastric cancer who may be candidates for bimodal treatment strategies:
FLOT3. Presenting Author: Salah-Eddin Al-Batran, Krankenhaus Nordwest,
UCT-University Cancer Center, Frankfurt, Germany
Background: The utility of surgery for metastatic gastric cancer is debated.
A prospective trial was performed to evaluate a prognostic model for
selecting patients (pts) treated with systemic chemotherapy (ct) who may
also be candidates for surgical intervention. Methods: Using a predefined
algorithm pts with untreated gastric cancer were prospectively stratified
into 3 groups: operable (OD), limited metastatic (LD), or extensive
metastatic (ED) disease and treated with 5-FU, oxaliplatin, leucovorin and
docetaxel (FLOT). LD was defined as: distant intra-abdominal lymph node
metastases only or/and a maximum of 1 organ involved, normal serum
alkaline phosphatase, � 5 liver lesions, no visible carcinomatosis (peritoneum
or pleura), and ECOG � 1. All other metastatic pts were ED. Pts with
OD received 4 preoperative ct cycles followed by surgery and 4 postoperative
cycles. Pts with LD received 8 cycles with surgery allowed for complete
macroscopic resection. Pts with ED received 8 cycles with surgery allowed
for palliation only. The study had 80% power to detect a HR of 0.55 for
overall survival in favor of the LD group (vs. ED group; 2-sided log-rank
p�0.05). Results: 238 of 252 pts included were eligible (OD/LD/ED:
51/60/127). LD pts had distant lymph nodes only (41%), liver (22%), lung
(17%), localized peritoneal involvement (7%), or others (13%). A median
of 8 ct cycles was applied to all groups. Median OS was 22.9 vs. 10.7
months in pts with LD vs. ED, respectively (HR 0.37; 95% CI, 0.25 – 0.56;
p �0.001). LD was the strongest predictor of OS in the multivariate
analysis including all single determinants of LD status (p�.002). Surgical
resection was conducted in 96%, 62%, and 12% in the OD, LD, and ED
groups, of which R0 resection (primary) was achieved in 82%, 81% and
33%, respectively. Within the LD arm, operated pts had better outcome
than non-operated pts (median OS 31.3 vs. 15.9 months; p�.004) and pts
with lymph node only involvement had best outcome. Conclusions: This
clinical model identifies a subset of pts with (limited) metastatic gastric
cancer who have a favorable outcome and who may be candidates for
bi-modal treatment strategies.
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