Maintenance Capecitabine-Bevacizumab Prolongs Time to Second Progression in Metastatic Colorectal Cancer in Dutch Trial
In the phase III CAIRO3 trial reported in The Lancet, Simkens et al of the Dutch Colorectal Cancer Group found that maintenance capecitabine-bevacizumab (Avastin) prolonged the time to second progression vs observation in patients with metastatic colorectal cancer.
In this open-label trial, 558 patients with previously untreated metastatic disease with at least stable disease after induction with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) were randomly assigned between May 2007 and October 2012 to maintenance capecitabine-bevacizumab (n = 279) or observation (n = 279). Maintenance consisted of capecitabine 625 mg/m2 twice daily continuously plus bevacizumab 7.5 mg/kg every 3 weeks. Disease status was assessed every 9 weeks. At progression (first progression), patients again received CAPOX-B until subsequent progression (second progression). Progression-free survival for second progression assessed from the time of randomization was the primary endpoint.
Increased Time to Progression
Median follow-up was 48 months. Median progression-free survival for second progression was 11.7 months in the maintenance group vs 8.5 months in the observation group (hazard ratio [HR] = 0.67, P < .0001). After first progression, 47% of maintenance group patients and 60% of the observation group received CAPOX-B. Median time to second progression on any treatment was 13.5 vs 11.1 months (HR = 0.68, P < .0001).
Adverse Events
Grade 3 or 4 adverse events occurred in 60% of the maintenance group vs 34% of the observation group (P < .0001), with hypertension (24% vs 18% grade 3), hand-foot skin reaction (23% vs 0% grade 3), sensory neuropathy (10% vs 5% grade 3, with one grade 4 event in the observation group), and hyperbilirubinemia (5% vs 0% grade 3, with one grade 4 event in the observation group) being more common in the maintenance group.
Global quality of life, assessed by the EORTC QLQ-C30 questionnaire, did not decrease during maintenance treatment, and no clinically significant differences were observed between groups.
The investigators concluded: “Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life.”
Miriam Koopman, MD, of the University Medical Center Utrecht, is the corresponding author of the Lancet article.
The study was supported by the Dutch Colorectal Cancer Group, Commissie Klinische Studies of the Dutch Cancer Foundation, Roche, and Sanofi-Aventis. For full disclosures of the study authors, visit www.thelancet.com.
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