A combination of maintenance bevacizumab (Avastin) plus standard second-line chemotherapy appears to be an effective strategy in managing patients with metastatic colorectal cancer (mCRC) after disease progression, according to the results of a phase III trial reported in Lancet
The open-label, multicenter study involved 820 patients with unresectable mCRC whose disease progressed within three months after discontinuing firstline bevacizumab plus chemotherapy. They were randomized to receive bevacizumab 2.5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, intravenously). plus second-line chemotherapy (n = 409) or chemotherapy alone (n = 411).
In this study, if a patient received oxaliplatin-based chemotherapy in the first-line setting, he received irinotecan-based chemotherapy in the second-line setting, and vice versa. The primary endpoint was overall survival (OS), analyzed by intention to treat.
The study found that the median overall survival (OS) in the bevacizumab combination arm was 11.2 months (95% CI, 10.4–12.2) and 9.8 months (95% CI, 8.9–10.7) in the chemotherapy-alone arm (HR = 0.81; 95% CI, 0.69– 0.94; unstratified log-rank test P = .0062). The median progression-free survival (PFS) was 5.7 months (95% CI, 5.2–6.2) in the bevacizumab arm and 4.1 months (95% CI, 3.7–4.4) in the chemotherapy-alone arm (HR = 0.68; 95% CI, 0.59–0.78; unstratified log rank P
The grade 3-5 adverse events that were more common in the bevacizumab combination arm versus the chemotherapy-alone group were, respectively, bleeding or hemorrhage (8 [2%] vs 1 [<1%]), gastrointestinal perforation (7 [2%] vs 3 [<1%]), and venous thromboembolism (19 [5%] vs 12 [3%]). The most frequently reported grade 3-5 adverse events in the bevacizumab combination versus chemotherapy-alone group were, respectively, neutropenia (65 [16%] vs 52 [13%]), diarrhea (40 [10%] vs 34 [8%]), and asthenia (23 [6%] vs 17 [4%]). The authors noted that the safety profile of the bevacizumab and chemotherapy combination was consistent with previously reported data in bevacizumab-naïve patients, and there were not substantial differences in toxicity between the two groups in this study.
“The results from this study could serve as proof of principle that maintaining angiogenesis inhibition while switching chemotherapy from the first and second lines in colorectal cancer has clinical benefits in patients,” the authors wrote.
The FDA approved bevacizumab as a first-line treatment for mCRC in 2004 and expanded the indication two years later to include second-line therapy in combination with 5-fluorouracil-based chemotherapy.
1. Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial [published online ahead of print November 16, 2012]. Lancet. doi:10.1016/S1470-2045(12)70477-1.