Using the drug bevacizumab (Avastin) in combination with chemotherapy or biological therapy raises the risk of treatment-related death—but the agent’s potential benefits may outweigh the relatively low absolute risk.

Bevacizumab, a humanized monoclonal antibody that inhibits tumor angiogenesis, is approved for treating—in combination with chemotherapy—advanced forms of colorectal, non-small-cell lung, and breast cancers; renal cell carcinoma; and glioblastoma multiforme. Bevacizumab has been associated with fatal adverse events, but its role in treatment-related mortality has been unclear.

Recently, however, Vishal Rampura, MD, of Stony Brook (New York) University Medical Center, and colleagues conducted a meta-analysis of 16 published randomized controlled trials involving a total of 10, 217 patients with a variety of advanced solid tumors. They found the overall incidence of fatal adverse events with bevacizumab to be 2.5%, and that compared with chemotherapy or biological therapy alone, the addition of bevacizumab increased the risk of fatal adverse events by a relative risk of 1.46 (148 fatal adverse events in the bevacizumab patients vs. 72 in the control groups). This association varied significantly with chemotherapeutic agents but not with tumor types of bevacizumab doses: The drug was linked to a 3.5-times higher risk of fatal adverse events in persons receiving taxanes or platinum agents, but was not associated with greater risk of fatal adverse events when used with other agents.  

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Nevertheless, “Given that the absolute risk of treatment-related mortality appears low, the use of bevacizumab should be considered in the context of overall survival benefits,” advise the authors (JAMA. 2011;305:487-494). “Because bevacizumab is increasingly used in cancer patients, it is particularly important for all health care practitioners and patients to understand and recognize the risk of treatment-related mortality.”

The investigators suggest minimizing this risk by:

  • selecting appropriate patients for bevacizumab therapy
  • using prophylactic granulocyte colony-stimulating factor
  • carefully monitoring bevacizumab patients for bleeding, neutropenia, and GI tract perforation (the most common causes of the fatal adverse events studied)
  • assessing patients early for toxic effects
  • properly managing serious adverse events.