- Cochrane Database Syst Rev. 2009 Jul 8;(3):CD005392.
Anti-angiogenic therapies for metastatic colorectal cancer.
Wagner AD, Arnold D, Grothey AA, Haerting J, Unverzagt S.
du Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier
Universitaire Vaudois, Rue du Bugnon 46, Lausanne, Switzerland, 1011.
Angiogenesis inhibitors have been developed to block tumour
angiogenesis and target vascular endothelial cells. While some of them
have already been approved by the health authorities and are
successfully integrated into patient care, many others are still under
development, and the clinical value of this approach has to be
OBJECTIVES: To assess the efficacy and toxicity of
targeted anti-angiogenic therapies, in addition to chemotherapy, in
patients with metastatic colorectal cancer. Primary endpoints are both
progression-free and overall survival. Response rates, toxicity and
secondary resectability were secondary endpoints. Comparisons were
first-line chemotherapy in combination with angiogenesis inhibitor, to
the same chemotherapy without angiogenesis inhibitor; and second-line
chemotherapy, to the same chemotherapy without angiogenesis inhibitor.
SEARCH STRATEGY: We searched the Cochrane Central Register of
Controlled Trials, MEDLINE, as well as proceedings from ECCO, ESMO and
ASCO until November 2008. In addition, reference lists from trials were
scanned, experts in the field and drug manufacturers were contacted to
obtain further information. SELECTION CRITERIA: Randomized controlled
trials on targeted anti-angiogenic drugs in metastatic colorectal
cancer (MCRC). DATA COLLECTION AND ANALYSIS: Data collection and
analysis was performed, according to a previously published protocol.
Because individual patient data was not provided, aggregate data had to
be used for the analysis. Summary statistics for the primary endpoints
were hazard ratios (HR's) and their 95% confidence intervals.
RESULTS: At present, eligible first line trials for this meta-analysis
were available for bevacizumab (5 trials including 3101 patients) and
vatalanib (1 trial which included 1168 patients). The overall HR s for
PFS (0.61, 95% CI 0.45 - 0.83) and OS (0.81, 95% 0.73 - 0.90) for the
comparison of first-line chemotherapy, with or without bevacizumab,
confirms significant benefits in favour of the patients treated with
bevacizumab. However, the effect on PFS shows significant
heterogeneity. For second-line chemotherapy, with or without
bevacizumab, a benefit in both PFS (HR 0.61, 95% CI 0.51 - 0.73) and OS
(HR 0.75, 95% CI 0.63-0.89) 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 and OS. AUTHORS'
CONCLUSIONS: The addition of
bevacizumab to chemotherapy of metastatic colorectal cancer prolongs
both PFS and OS in first-and second-line therapy.