Continuation or Reintroduction of Bevacizumab Improves Outcomes in Colorectal Cancer

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The standard first-line treatment for metastatic colorectal cancer (mCRC) is the combination of bevacizumab, a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), and fluorouracil-based chemotherapy.

Two cohort studies (BRiTE and ARIES) and preclinical models have demonstrated that when established tumors are exposed to an anti-VEGF antibody for a longer period of time, it can delay tumor growth and extend survival. 

Investigators sought to determine the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after the first progression in patients with mCRC. Two randomized trials were conducted: ML18147 trial and BEBYP trial; both studies were interrupted prematurely.

There were 185 patients treated with bevacizumab plus fluorouracil-based chemotherapy and were randomized to receive either second-line chemotherapy (mFOLFOX-6 or FOLFIRI) with or without bevacizumab. The primary end-point was progression-free survival, and 262 patients were needed to detect a hazard ration (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively.

At a median follow-up of 45.3 months, the median progression free survival was 5.0 months in the chemotherapy-group and 6.8 months in the bevacizumab-group (adjusted HR=0.70; 95%CI 0.52-0.95; p=0.010). A subgroup analyses showed an enhanced overall survival in the bevacizumab group (adjusted HR=0.77; 95%CI 0.56-1.06; p=0.043).

Overall, the authors concluded that the continuation or the reintroduction of bevacizumab with second-line chemotherapy improves the outcome of patients with progressive mCRC, and thus support this strategy for the treatment of mCRC. 

Adding everolimus to paclitaxel, trastuzumab does not significantly prolong PFS in breast cancer.
Standard treatment for mCRC is combination bevacizumab and fluorouracil-based chemotherapy.
The authors studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy.
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