Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: Results of a randomised Phase 2 study

Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients. Methods The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel + oxaliplatin (DOCOX) = docetaxel 60 mg/m² plus oxaliplatin 130 mg/m² on Day 1 of each 21-day cycle. Arm 2: docetaxel + oxaliplatin + cetuximab (DOCOX + C) = DOCOX with C 400 mg/m² first dose then 250 mg/m² weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status. Findings One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX + C: gastric 44%/41%, gastroesophageal junction 51%/55%, both 5%/4%. Response rate/arm: 26.5%/38.0%. Median progression-free survival: 4.7/5.1 months (95% confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1%/33.0%, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6 months. Grade 3-4 treatment-related adverse events (%) included neutropenia (50%/44%), febrile neutropenia (13%/19%), diarrhoea (12%/17%), fatigue (12%/17%) and leukopenia (7%/14%). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings. Interpretation Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.