Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study

Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H-917, New York, NY 10021, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 05/2008; 26(12):2013-9. DOI: 10.1200/JCO.2007.14.9930
Source: PubMed


To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).
Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS).
A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials.
The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.

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Available from: Florin Sirzén, Mar 23, 2014
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    • "months in the 5-FU/LV plus bevacizumab group despite the absence of oxaliplatin, compared with 5.2–5.5 months in the 5-FU/LV group. While no study has directly compared FOLFOX plus bevacizumab with 5-FU/LV plus bevacizumab, the results of previous clinical trials [3] [9] [10] indicate that the median PFS is similar with these regimens, and that 5-FU/LV plus bevacizumab is better tolerated, with a lower incidence of adverse events. These clinical results suggest that it may be unnecessary to use oxaliplatin or irinotecan in combination with 5-FU as first-line treatment and that sequential chemotherapy based on 5-FU is useful. "
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