Background: To investigate the efficacy and safety of bevacizumab beyond first progression combined with doublet chemotherapy in patients with metastatic colorectal cancer.
Methods: This multicenter phase II study included 76 patients with metastatic colorectal cancer progressed after first-line bevacizumab plus doublet chemotherapy. Study treatment consisted of second-line continuation of bevacizumab plus crossover standard doublet chemotherapy, consisting of FOLFOX, CapeOX, or FOLFIRI. Bevacizumab was administered in doses of 5 mg/kg/2-week or 7.5 mg/kg/3-week according to the schedules of the combined regimen.
Results: Median progression-free survival (PFS) and overall survival (OS) was 6.5 months (95 % CI, 5.2-7.8) and 12.8 months (95 % CI, 8.8-16.9), respectively, with no significant differences according to combined doublet chemotherapy. The response rate (RR) was 17.1 % (95 % CI, 8.6-5.6) with no statistical significance between regimens (p = 0.053). The first-line RR and PFS did not affect the second-line efficacy outcomes; RR (14.0 % vs 21.2 %, p = 0.405), median PFS (5.6 vs 6.7 months, p = 0.335), and OS (15.4 vs 11.0 months, p = 0.383) were not different between previous responders and non-responders, and the median PFS (p = 0.186) and OS (p = 0.495) were not different either according to the length of first-line PFS; however, OS from the first-line chemotherapy was longer in patients with longer first-line PFS (26.4 vs 14.8 months, p = 0.010). Bevacizumab-related significant adverse events included proteinuria (1.3 %) and thromboembolism (1.3 %).
Conclusions: Bevacizumab beyond first progression could be considered a treatment strategy even in patients progressed after first-line bevacizumab plus doublet chemotherapy. Second-line efficacy outcomes did not differ according to the first-line responses.