(ChemotherapyAdvisor) – Patients with metastatic colorectal cancer derive clinical benefits when VEGF inhibition is maintained with bevacizumab plus standard second-line chemotherapy beyond disease progression, phase 3 trial results reported in the January 2013 issue of the Lancet Oncology.
These results indicate “a new proof of principle in antiangiogenic treatment for cancer,” noted Jaafar Bennouna, MD, Institut de Cancérologie de l’Ouest, Nantes, France, on behalf of the ML18147 Study Investigators.
Between February 1, 2006 and June 9, 2010, the open-label study randomly assigned patients with unresectable, histologically confirmed metastatic colorectal cancer who had disease progression up to 3 months after discontinuing first-line bevacizumab plus chemotherapy to either second-line chemotherapy plus bevacizumab 2.5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, intravenously; n=409) or chemotherapy alone (n=411).
Median follow-up was 11.1 months in the bevacizumab-plus-chemotherapy group and 9.6 months in the chemotherapy-alone group.
Median overall survival was 11.2 months (95% CI: 10.4-12.2 months) for patients in the bevacizumab-plus-chemotherapy arm versus 9.8 months (95% CI: 8.9-10.7) for those in the chemotherapy-alone arm (hazard ratio 0.81; 95% CI: 0.69-0.94; unstratified log-rank test P=0.0062).
Grade 3−5 adverse events (AEs) that occurred more frequently in the bevacizumab-plus-chemotherapy arm were bleeding or hemorrhage, gastrointestinal perforation, and venous thromboembolisms; most frequently reported grade 3−5 AEs were neutropenia, diarrhea, and asthenia. Four patients in the bevacizumab-plus-chemotherapy group and three in the chemotherapy-alone group died on treatment.
“Our results show that bevacizumab continued beyond disease progression, while switching chemotherapy is beneficial for patients with metastatic colorectal cancer who were previously treated with bevacizumab in the first-line setting,” Dr. Bennouna stated. “The continued use of bevacizumab beyond disease progression leads to a significant improvement in overall survival and progression-free survival compared with post-progression chemotherapy alone.”
This study was funded by F. Hoffmann-La Roche.