Analysis of biomarker expression (ki67, EGFR, HER2, ERK, NFkB, and mTOR) in patients with advanced gastric and gastroesophageal junction (GEJ) cancer treated with cetuximab plus cisplatin/docetaxel: DOCETUX study.

Abstract

4133 Background: The aim of this study was to evaluate the correlation between pathologic biomarkers and objective response (OR), time-to-progression (TTP) and overall survival (OS) in advanced gastric or GEJ cancer patients (pts) treated with cetuximab plus chemotherapy. Methods: We analysed 31/72 pts with gastric or GEJ locally advanced/metastatic adenocarcinoma enrolled in the DOCETUX Study (Pinto et al., Br. J. Cancer, 2009). The pts were treated as first-line with cetuximab weekly plus cispatin/docetaxel every 3 weeks, for a maximum of 6 cycles, then cetuximab alone in pts with CR/PR/SD. In these pts KRAS/BRAF mutations were infrequent and not associated with efficacy (Stella et al., ASCO 2009, Abs 15503). Analyses of ki67, EGFR, HER2, ERK, NFkB and mTOR were performed using immunohistochemistry on primary tumor by just one pathologist. Results: Pt characteristics: 27M/4F; median age 62 years (24-74); stomach 28 (90.3%), GEJ 3 (9.7%); intestinal histotype 24 (77.4%), nonintestinal 7 (22.6%); locally advanced disease 1(3.2%), metastatic disease 30(96.8.%). OR were: 15 (48.4%) CR+PR, 10 (32.3%) SD, 4 (12.9%) PD, 2 (6.5%) NE. Median TTP was 5 months (1-23), and median OS 11 months (1-26). The expression of pathological biomarkers was: ki67 > 40% in 83.9% of pts, EGFR score high in 26.1%, HER2 2+-3+ in 28.6%, ERK > 30% in 48.4%, NFkB > 5% in 43.5% and mTOR > 2% in 58.1%. In the multivariate analysis, the better OR was observed in pts with negative/low EGFR (p = 0.017) and high ERK (p = 0.035), and a longer TTP in pts with positive mTOR (p = 0.036). Any other statistically significant correlation was observed. Conclusions: This results suggest that negative/low EGFR score, high ERK and positive mTOR expressions are correlated to treatment efficacy. No significant financial relationships to disclose.