Abstract
BackgroundBevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens.MethodsA wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen.ResultsSix trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS) and progression-free survival (PFS) (HR = 0.84; CI: 0.77-0.91; P < 0.00001 and HR = 0.72; CI: 0.66-0.78; P < 0.00001, respectively). However, heterogeneity of results was very high for both outcomes, and subgroup analyses supported the OS advantage with bevacizumab restricted to irinotecan-based regimens. Infusional fluorouracil subsets involved a minor proportion, and did not demonstrate statistical benefit in PFS or OS. Regarding toxicity, higher rates of grades 3-4 hypertension, bleeding, thromboembolic events and proteinuria were uniformly observed with bevacizumab, leading to increased treatment interruptions (HR = 1.47; P = 0.0004).ConclusionsBevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.
Highlights
Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer
The results indicated an advantage to the use of bevacizumab (HR = 0.84; 95% confidence intervals (CI): 0.77-0.91; P < 0.00001), though heterogeneity was observed (I2 = 60%; P = 0.04)
The second explanation is a possible interaction of cytotoxic agents with vascular endothelial growth factor (VEGF)-inhibitors like bevacizumab
Summary
Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. Clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate the efficacy of bevacizumab, and the impact of divergent backbone regimens. One of the Bevacizumab in colorectal cancer was studied initially in the metastatic setting, and was approved by US Food And Drug Administration (FDA) in 2004, based on a survival benefit noted in the AVF2107 trial [5] with the Saltz’ irinotecan, 5-fluorouracil and leucovorin (IFL) regimen [6]. One of the most mentioned studies regarding oxaliplatin-based chemotherapy is a prospective, double-blind randomised trial of 1400 patients evaluating bevacizumab and the FOLFOX or XELOX regimen in first-line treatment [8]. The benefit on OS with the use of oxaliplatin is limited to the second-line setting, applying higher doses of bevacizumab [9]
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