Anti-angiogenic therapies for metastatic colorectal cancer (MCRC): Preliminary results of a systematic review and meta-analysis

Abstract

4060 Background: Anti-angiogenesis is one of the most exciting approaches in drug development. However, results from individual trials in MCRC are highly variable and the clinical value of this strategy needs further clarification. Therefore our objective was to assess the effect of targeted anti-angiogenic therapies in addition to chemotherapy (ctx) in patients (pts) with MCRC. Methods: Systematic review and meta-analysis were performed on the basis of a previously published protocol. Progression-free (PFS) and overall survival (OS) were primary endpoints, with OS being hierachically lower ranked. Response rates, toxicity and secondary resectability were secondary endpoints. Search strategy: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, proceedings from ECCO, ESMO, ASCO until 11/ 2007. Selection criteria: Randomized controlled trials on targeted anti-angiogenic drugs in MCRC. As individual patient data was not provided, aggregate data had to be used for the analysis. Results: 5 eligible trials using bevacizumab (bev) were identified (4 in 1st-line, 1 in 2nd- line). 1 trial was excluded due to insufficient data. The pooled HR’s for PFS and OS for the comparison of ctx with versus without bev (4 trials, 2999 pts) were 0.68 [95% CI 0.62 -0.74] and 0.79 [95% CI 0.73–0.87] in favour of the pts treated with bev. When only trials comparing 1st line ctx with versus without bev were included (3 trials, 2422 pts), the pooled HR’s for PFS and OS were 0.70 [95% CI 0.63–0.76] and 0.81 [95% CI 0.73–0.90]. The odds ratios (OR) for all-cause 60-day mortality (n=2,935 pts, OR= 0.790; 95% CI 0.53–1.18) and treatment-related deaths (n=2,335 pts, OR 0.99; 95% CI 0.58–1.68) had insignificant results. Two phase III trials using PTK787/ZK 222584 in 1st- and 2nd-line have been published, but final results are available for only one of them at present and will be included in the future for this reason. Conclusions: The addition of bev to ctx significantly improves PFS and OS in MCRC, although the initially observed magnitude of the treatment effect could not be reproduced in later studies. Supported by BMBF [FKZ 01 KG 0603]. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Roche Roche, sanofi-aventis Genentech™ BioOncology, Roche