Cetuximab is Associated With Excessive Toxicity When Combined With Bevacizumab Plus mFOLFOX6 in Metastatic Colorectal Carcinoma

Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/eucovorin/oxaliplatin) as first-line therapy for mCRC. Patients and Methods: Sixty-six patients received cetuximab (400 mg/m(2) loading dose, then 250 mg/m(2) weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity. Results: The most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity. Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase Ill trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.