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

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260s Gastrointestinal (Noncolorectal) Cancer<br />

4087 General Poster Session (Board #46F), Mon, 8:00 AM-12:00 PM<br />

Tolerability and efficacy <strong>of</strong> a biweekly docetaxel, fluorouracil, leucovorin,<br />

oxaliplatin regimen (TFOX) in previously advanced metastatic gastric and<br />

oesogastric junction (AGC) adenocarcinoma. Presenting Author: Simon<br />

Pernot, Hôpital Européen Georges Pompidou, Paris, France<br />

Background: The DCF regimen is superior to 5-FU-Cisplatin in term <strong>of</strong><br />

response rate (RR) and overall survival (OS) in advanced gastric cancer, but<br />

is also more toxic. Oxaliplatin is better tolerated and can effectively replace<br />

cisplatin in AGC patients (pts). We hypothesize that incorporating Docetaxel<br />

into a simplified FOLFOX regimen should be a tolerable and<br />

efficient option, and could facilitate the use <strong>of</strong> this drug in 1st line in AGC.<br />

Methods: TFOX regimen was given biweekly as follow: Docetaxel (50mg/<br />

m2), oxaliplatin (85mg/m2), leucoverin (400mg/m2) and 5FU continuous<br />

infusion 48h (2400mg/m2). Main inclusion criteria were: pts with histollogically<br />

proven metastatic or locally advanced gastric or oesogastric junction<br />

adenocarcinoma, previously untreated, PS�2. Using Fleming design the<br />

primary end point was response rate, needing a sample size <strong>of</strong> 40 pts.<br />

Results: Between 02/2008 and 07/2011, 41 pts with AGC were enrolled<br />

(oesogastric junction: 17 pts, diffuse type: 22 pts, metastatic: 37 pts);<br />

mean age was 53.5 years (31-73), 26 pts were male. PS 0/1/2: 11/24/6<br />

pts, 14 pts had a relapse after a R0 resection. The total number <strong>of</strong> cycles<br />

administered was 310 (mean 7.6 cycles/pts) and 90% <strong>of</strong> pts received at<br />

least 4 cycles. No toxic death occurred. Grade 3-4 toxicities were observed<br />

in 20 pts (48%). Grade 3-4 toxicities were neutropenia (29%) febrile<br />

neutropenia (7%), neurotoxicity (10%), asthenia (10%). ORR was 63%<br />

(n�26) [IC95% 48-78], with 2 complete responses. Disease control rate<br />

(CR�PR�SD) was 78% (n�32) [IC95% 65-90]. Median progression free<br />

survival and overall survival were 6.5 months [IC95% 5.02-10.85] and<br />

12.1 months [IC95% 7.25-15.28], respectively. Conclusions: TFOX is<br />

effective with a manageable toxicity pr<strong>of</strong>ile in first line treatment for AGC<br />

pts. Tolerability <strong>of</strong> this regimen compares favourably with DCF reported<br />

tolerability. TFOX may be an alternative option for intensive 1st line<br />

treatment and should now be evaluated in randomized trials.<br />

4089 General Poster Session (Board #46H), Mon, 8:00 AM-12:00 PM<br />

Assessment <strong>of</strong> HER2 status from an epidemiology study in tumor tissue<br />

samples <strong>of</strong> gastric and gastro-esophageal junction cancer: Spanish results<br />

<strong>of</strong> the HER-EAGLE study. Presenting Author: Lourdes Gomez, Hospital<br />

Virgen del Rocío, Sevilla, Spain<br />

Background: Overexpression <strong>of</strong> HER2 is an important biomarker in gastroesophageal<br />

junction (GEJ) and gastric cancer (GC) and a predictive factor<br />

for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit<br />

in overall survival <strong>of</strong> adding trastuzumab to chemotherapy inHER2-positive<br />

advanced GEJ/GC patients, following validated scoring criteria by a central<br />

laboratory. This study examines the incidence <strong>of</strong> HER2 positivity (local<br />

laboratories) in GEJ/GC according to EMA Herceptin label. Methods:<br />

HER-EAGLE was an epidemiological, non–interventional, international<br />

study assessing HER2 status by IHC/ISH in tumor samples from any stage<br />

GEJ/GC patients. Neutral buffered 10% formalin embedded tissues (surgical<br />

excision specimens or minimum 6-8 biopsies) analyzed via validated<br />

Ventana and Dako methods and scoring criteria used in ToGA: HER2positive<br />

if IHC 3� or IHC 2� (FISH/SISH confirmed; HER2/CEP17 ratio �<br />

2.0); HER2-negative if IHC 0 or IHC 1�. Overall and subgroup estimates<br />

calculated with 95%CI. Data from the Spanish cohort are presented.<br />

Results: The Spanish cohort <strong>of</strong> HER-EAGLE included 1,954 participants<br />

(63.7% males) from 33 hospitals (Dec2010 to Aug2011), with 469<br />

biopsies (24.0%) and 1,479 excisions (75.7%). Samples were 13.7% GEJ<br />

and 86.3% GC, and the adenocarcinomas were 1,137 intestinal (58.2%),<br />

510 diffused (26.1%), 163 mixed (8.3%; Laureen classification), and 144<br />

not available (7.3%). Median time from sampling to HER2 analysis <strong>of</strong> 5.1<br />

years (range from days to 12 years). Total <strong>of</strong> 210 cases tested IHC 3�<br />

(10.7%), 215 IHC 2� (11.0%), 308 IHC 1� (15.8%), and 1,221 IHC 0<br />

(62.5%). Overall, HER2 positivity (IHC 3� or IHC2�/ISH�) was 14.1%<br />

(95%CI 12.61 – 15.75). HER2 positivity by histological type was higher in<br />

intestinal adenocarcinomas (19.5%) compared to diffused (4.5%) or in<br />

mixed (9.2%). Conclusions: HER-EAGLE confirmed the feasibility <strong>of</strong><br />

community based HER2 testing in GC as the first study with a high number<br />

<strong>of</strong> samples analyzed by local laboratories. The incidence <strong>of</strong> HER2-positivity<br />

(EMA label definition) was similar to the ToGA screening population, and it<br />

was again higher in adenocarcinomas <strong>of</strong> intestinal type (19.5%).<br />

4088 General Poster Session (Board #46G), Mon, 8:00 AM-12:00 PM<br />

Prognostic value <strong>of</strong> lemur tyrosine kinase-3 (LMTK3) polymorphism in<br />

Japanese (J) patients (PTS) with localized gastric adenocarcinoma (GAC).<br />

Presenting Author: Afsaneh Barzi, Norris Comprehensive Cancer Center,<br />

University <strong>of</strong> Southern California, Los Angeles, CA<br />

Background: LMTK3 is an estrogen receptor � (ER�) regulator. Recent<br />

studies show that [rs808419(r8) and rs9989661(r9)] and LMTK3 expression<br />

are prognostic in breast and colon cancers. Our group demonstrated<br />

that r9AA is associated with shorter time to recurrence in Caucasian(C) and<br />

Hispanic(H) females(F) with GAC. We investigated the significance <strong>of</strong><br />

LMTK3 polymorphism in J PTS with GAC. Methods: Blood or tissue samples<br />

<strong>of</strong> 169 J PTS who had surgery with/without adjuvant chemotherapy (ACT)<br />

were analyzed. Genomic DNA was extracted using the QIAmp kit; all<br />

samples were analyzed using PCR-based direct DNA-sequencing. The<br />

endpoints <strong>of</strong> the study were disease-free survival (DFS) and overall survival<br />

(OS). Kaplan-Meier curves and log-rank test were used for univariate<br />

analysis. Multivariate analysis was performed to test the interaction<br />

between polymorphism and gender adjusting for other variables. Results:<br />

60 F and 109 males were enrolled in this study, 17% stage(s) IB, 31% s II,<br />

36% s III, 17% s IV (AJCC-6). The median age was 67(31-88). 65% <strong>of</strong> PTS<br />

received S-1 based ACT. Median follow-up was 4 years(ys). Prognosis was<br />

worse in men with r9 AA than AG/GG, at 1 year 67% (95% CI 40-83%) with<br />

AA vs 99% (95% CI 91-99%) <strong>of</strong> AG/GG were alive (p� 0.039). Median<br />

survival was not reached in the AG/GG group; in the AA group median DFS<br />

and OS was 1yr (p� 0.03) and 2ys (p� 0.039) respectively. In the<br />

multivariate analysis adjusting for s, age, and ACT, males carrying AA had<br />

increased risk <strong>of</strong> disease recurrence (HR 3.84 95%CI 1.86-7.92, p�<br />

0.001) and dying (HR 3.47 95%CI 1.58-7.62 p�0.002) compared to<br />

those with AG/GG (HR�1, reference). Conclusions: r9 AA was associated<br />

with significantly worse DFS and OS in J male with GAC. These results<br />

confirm our previous findings that LMTK3 is an independent prognostic<br />

factor for localized GAC; interestingly the relationship between gender and<br />

prognostic significance is the opposite in J vs. C/H. The gender disparity<br />

can be due to the differences in the etiology (histological subtypes),<br />

management strategies, allele frequency, and degree <strong>of</strong> estrogen exposure<br />

in the two populations. Additional studies are warranted to identify the<br />

underlying biological mechanism.<br />

4090 General Poster Session (Board #47A), Mon, 8:00 AM-12:00 PM<br />

A prospective trial for defining a subset <strong>of</strong> patients with limited metastatic<br />

gastric cancer who may be candidates for bimodal treatment strategies:<br />

FLOT3. Presenting Author: Salah-Eddin Al-Batran, Krankenhaus Nordwest,<br />

UCT-University Cancer Center, Frankfurt, Germany<br />

Background: The utility <strong>of</strong> surgery for metastatic gastric cancer is debated.<br />

A prospective trial was performed to evaluate a prognostic model for<br />

selecting patients (pts) treated with systemic chemotherapy (ct) who may<br />

also be candidates for surgical intervention. Methods: Using a predefined<br />

algorithm pts with untreated gastric cancer were prospectively stratified<br />

into 3 groups: operable (OD), limited metastatic (LD), or extensive<br />

metastatic (ED) disease and treated with 5-FU, oxaliplatin, leucovorin and<br />

docetaxel (FLOT). LD was defined as: distant intra-abdominal lymph node<br />

metastases only or/and a maximum <strong>of</strong> 1 organ involved, normal serum<br />

alkaline phosphatase, � 5 liver lesions, no visible carcinomatosis (peritoneum<br />

or pleura), and ECOG � 1. All other metastatic pts were ED. Pts with<br />

OD received 4 preoperative ct cycles followed by surgery and 4 postoperative<br />

cycles. Pts with LD received 8 cycles with surgery allowed for complete<br />

macroscopic resection. Pts with ED received 8 cycles with surgery allowed<br />

for palliation only. The study had 80% power to detect a HR <strong>of</strong> 0.55 for<br />

overall survival in favor <strong>of</strong> the LD group (vs. ED group; 2-sided log-rank<br />

p�0.05). Results: 238 <strong>of</strong> 252 pts included were eligible (OD/LD/ED:<br />

51/60/127). LD pts had distant lymph nodes only (41%), liver (22%), lung<br />

(17%), localized peritoneal involvement (7%), or others (13%). A median<br />

<strong>of</strong> 8 ct cycles was applied to all groups. Median OS was 22.9 vs. 10.7<br />

months in pts with LD vs. ED, respectively (HR 0.37; 95% CI, 0.25 – 0.56;<br />

p �0.001). LD was the strongest predictor <strong>of</strong> OS in the multivariate<br />

analysis including all single determinants <strong>of</strong> LD status (p�.002). Surgical<br />

resection was conducted in 96%, 62%, and 12% in the OD, LD, and ED<br />

groups, <strong>of</strong> which R0 resection (primary) was achieved in 82%, 81% and<br />

33%, respectively. Within the LD arm, operated pts had better outcome<br />

than non-operated pts (median OS 31.3 vs. 15.9 months; p�.004) and pts<br />

with lymph node only involvement had best outcome. Conclusions: This<br />

clinical model identifies a subset <strong>of</strong> pts with (limited) metastatic gastric<br />

cancer who have a favorable outcome and who may be candidates for<br />

bi-modal treatment strategies.<br />

Visit abstract.asco.org and search by abstract for the full list <strong>of</strong> abstract authors and their disclosure information.

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