Results of docetaxel plus oxaliplatin (DOCOX) with or without cetuximab in patients with metastatic gastric and/or gastroesophagel junction adenocarcinoma: Results of a randomized phase II study.

Abstract

4015 Background: Advanced adenocarcinoma of the gastroesophageal junction and/or stomach is standardly treated by combination chemotherapy with minimal improvements in survival. This study evaluated the value of adding cetuximab (C) to combination chemotherapy in this disease. Methods: The primary objective of this noncomparative study was progression-free survival (PFS); secondary objectives were 1-yr survival, response rate, time to response (TTR), duration of response (DOR), and safety. Treatment (Tx): Arm 1: DOCOX = docetaxel 60 mg/m2 plus oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. Arm 2: DOCOX + C = DOCOX with C 400 mg/2 1st dose, then 250 mg/m2weekly. Key inclusion: stage IV adenocarcinoma of the GEJ/stomach; measurable disease; ECOG 0-2; and normal renal, hepatic, and marrow function; exclusion: any prior Tx other than adjuvant radiation with 5-FU/leucovorin. Results: 150 pts enrolled; 75/arm. Demographics Arm 1/2: male 79%/80%, median age 61/64 yrs; disease site: gastric 44%/41%, GEJ 51%/55%, both 5%/4%; 93%/96% had surgery, 7%/5% had radiation. Response rates/arm: 24%/29%. Median PFS was 4.7/5.1 mos (ranges, <1-24.8/<1-10.4); 1-yr survival was 40%/32%, median overall survival was 9.0/8.5 months; median TTR was 1.3/1.3 mos, and median DOR was 13.8/7.2 mos. The most frequent grade 3-4 treatment-related adverse events (AEs) included: neutropenia (44%/40%) diarrhea and febrile neutropenia (12%/17%, each), and fatigue (10%/15%). Analysis of KRAS is ongoing. Conclusions: The addition of C to DOCOX may improve RR minimally; there appears to be no significant improvement in PFS, OS, or 1-year survival. C did not produce clinically significant benefit when added to the backbone of DOCOX. Toxicities were consistent with the known safety profiles of the study drugs. Supported in part by grants from sanofi-aventis, Bridgewater, NJ and Lilly/ImClone, Indianapolis, IN.