A Cochrane review included 6 studies with a total of 4 271 subjects; 5 studies of bevacizumab (n=3101) and 1 of vatalanib (n=1168) in combination with chemotherapy. Bevacizumab in combination with first-line chemotherapy appears to prolong both progression-free survival (PFS) (HR 0.61, 95% CI 0.45 to 0.83; 4 studies, n= 2526; increase in median progression-free survival from 7.1 to 9.7 months) and overall survival (OS) (HR 0.81, 95% CI 0.73 to 0.90; 4 studies, n= 2526; increase in median survival from 17.7 to 20.5 months) of patients with metastatic colorectal cancer, as compared to chemotherapy alone. However, the effect on PFS shows significant heterogeneity (I2= 84%). For second-line chemotherapy, with or without bevacizumab, a benefit in both PFS (HR 0.61, 95% CI 0.51 - 0.73; 1 study, n=559; increase in median progression-free survival from 4.7 to 7.3 months) and OS (HR 0.75, 95% CI 0.63-0.89; 1 study, n=577; increase in median survival from 10.8 to 12.9 months) was demonstrated in a single, randomized trial.
While differences in treatment-related deaths and 60-day mortality were not significant, higher incidences in grade III/IV hypertension, arterial thrombembolic events and gastrointestinal perforations were observed in the patients treated with bevacizumab.
For valatanib, currently available data showed a non-significant benefit in PFS (HR 0.89, 95% CI 0.78 to 1.03; 1 study, n=1168; increase in median progression-free survival from 7.7 to 9.1 months) and OS (HR 1.08, 95% CI 0.94 to 1.24; 1 study, n=1168; median survival times were 20.5 months for chemotherapy alone compared to 21.4 months with the addition of vatalanib).