Benefit of Maintenance Bevacizumab-Erlotinib vs Bevacizumab After Bevacizumab-Based Induction Therapy in Metastatic Colorectal Cancer
As reported by Tournigand et al in The Lancet Oncology, final analysis of the phase III GERCOR DREAM (OPTIMOX3) trial suggested a benefit of maintenance bevacizumab (Avastin)-erlotinib vs bevacizumab after bevacizumab-based induction therapy in patients with previously untreated metastatic colorectal cancer.
Study Details
The open-label study enrolled 700 patients in 49 centers in France, Austria, and Canada between January 2007 and October 2011. After bevacizumab-based induction therapy, 452 patients without disease progression were randomly assigned to receive bevacizumab at 7.5 mg/kg every 3 weeks plus erlotinib at 150 mg once daily (n = 224) or bevacizumab alone (n = 228). All patients were stratified by center, baseline performance status, age, and number of metastatic sites. The primary endpoint was progression-free survival on maintenance therapy on intention-to-treat analysis.
Progression-Free and Overall Survival
In the primary progression-free survival analysis (performed after the first 231 progression-free survival events), median progression-free survival duration from maintenance was 5.1 months (95% confidence interval [CI] = 4.1–5.9 months) in the bevacizumab-erlotinib group vs 6.0 months (95% CI = 4.6–7.9 months) in the bevacizumab group (stratified hazard ratio [HR] = 0.79, P = .11; unstratified HR = 0.76, P = .043). At final analysis, median follow-up was 48.3 months in the bevacizumab-erlotinib group and 51.0 months in the bevacizumab group.
At data cutoff for the final analysis (356 progression-free survival events), median progression-free survival from maintenance was 5.4 months (95% CI = 4.3–6.2 months) in the bevacizumab-erlotinib group vs 4.9 months (95% CI = 4.1–5.7 months) in the bevacizumab group (stratified HR = 0.81, P = .059; unstratified HR = 0.78, P = .019). Progression-free survival curves appeared to diverge after approximately 5 months in favor of bevacizumab-erlotinib. Median progression-free survival from study inclusion was 10.1 months vs 9.3 months.
At final analysis, median overall survival from maintenance was 24.9 months (95% CI = 21.4–28.9 months) in the bevacizumab-erlotinib group vs 22.1 months (95% CI = 19.6–26.7 months) in the bevacizumab group (stratified HR = 0.79, P = .036; unstratified HR = 0.79, P = .035).
Adverse Events
The most common grade 3 or 4 adverse events during maintenance treatment in the bevacizumab-erlotinib group were skin rash (21% vs 0%), diarrhea (10% vs < 1%), and asthenia (5% vs < 1%). Maintenance treatment was discontinued due to adverse events in 8% vs 3% of patients.
The investigators concluded: “Maintenance bevacizumab plus erlotinib might be a new non-chemotherapy-based maintenance option for the first-line treatment of patients with unresectable metastatic colorectal cancer after bevacizumab-based induction therapy.”
The study was funded by GERCOR and F. Hoffmann-La Roche.
Aimery de Gramont, MD, of Institut Hospitalier Franco-Britannique, Levallois-Perret, France, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
