First-Line Cetuximab vs Bevacizumab Plus Chemotherapy in KRAS Wild-Type Colorectal Cancer

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Alan Venook, MD

Alan Venook, MD

A phase III trial has shown no significant difference in overall survival with first-line cetuximab (Erbitux) vs bevacizumab (Avastin) plus chemotherapy in patients with advanced or metastatic KRAS wild-type colorectal cancer. These study findings were reported by Alan Venook, MD, of University of California, San Francisco, and colleagues in JAMA

The trial (Cancer and Leukemia B and SWOG 80405) underwent numerous amendments, including those restricting enrollment to patients with wild-type KRAS (after findings of a lack of efficacy of epidermal growth factor receptor [EGFR] inhibition in KRAS-mutant disease were reported) and dropped a cetuximab/bevacizumab combination arm (after failures of the dual-antibody approach were reported). After the 11th interim analysis concluded that neither treatment group could meet the preplanned goal of a 5.5-month difference in overall survival between groups, data were released by the Alliance data and safety monitoring board in January 2014. 

In the open-label trial, 1,137 patients enrolled at National Clinical Trials Network sites in the United States and Canada between November 2005 and March 2012 chose to receive mFOLFOX6 (leucovorin, fluorouracil, and oxaliplatin) or FOLFIRI (leucovorin, fluorouracil, and irinotecan) and were randomized to receive cetuximab (n = 578) or bevacizumab (n = 559). Randomization was stratified by chemotherapy regimen, receipt of prior adjuvant chemotherapy, and prior pelvic radiation. The primary endpoint was overall survival. The last date of follow-up was in December 2015. 

Efficacy Outcomes 

Median follow-up among surviving patients was 47.4 months. Median overall survival was 30.0 months in the cetuximab group vs 29.0 months in the bevacizumab group (stratified hazard ratio (HR) = 0.88, P = .08). Median progression-free survival was 10.5 months vs 10.6 months (stratified HR = 0.95, P = .45). Objective responses were observed in 59.6% vs 55.2% of patients (P = .13). 

The investigators concluded: “Among patients with KRAS [wild-type] untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.” 

The research reported in the JAMA article was supported by the National Cancer Institute. The trial was supported by Eli Lilly and Company, Genentech, Pfizer Inc, and Sanofi. ■

Venook A, et al: JAMA 317:2392-2401, 2017.




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