Bevacizumab tied to higher rate of fatal adverse events

Compared to those taking chemotherapy alone, patients who took bevacizumab (Avastin) in combination with chemo- or biological therapy had more fatal adverse events, according to a new meta-analysis.

The analysis included 16 randomized controlled trials and 10,217 patients with a variety of advanced solid tumors. The overall incidence of fatal adverse events in the bevacizumab patients was 2.5%, which translated into a 46% higher risk compared to chemotherapy alone (P=0.01). The most common fatal adverse events were hemorrhage (23.5%), neutropenia (12.2%) and gastrointestinal tract perforation (7.1%), although the study authors also noted a relatively large number of unspecified causes.

The risk of fatal adverse events differed depending on which class of chemotherapeutic agents patients received. Platinum and taxanes appeared to pose a higher risk, although the difference was not statistically significant. The analysis also indicated the possibility of a dose-dependent effect, because the association between bevacizumab and fatal adverse events was statistically significant at a dose of 5.0 mg/kg per week, but not at a dose of 2.5 mg/kg per week. However, the difference in effect between the two doses was not statistically significant.

The study authors noted that the absolute risk of treatment-related mortality was low and they called for the risks of bevacizumab to be considered in the context of overall survival benefits. They also recommended some approaches for reducing the risk of fatal adverse events in patients taking the drug, including monitoring patients carefully for the most common adverse events, using prophylactic granulocyte colony-stimulating factor, adequately managing serious adverse events and selecting appropriate patients for therapy.

The last suggestion may pose a challenge, according to the author of an accompanying editorial, who noted that “few insights are available about specific subgroups of patients who may benefit” from bevacizumab. The editorialist concluded that the “jury is still out” on the drug, and noted that although the drug may benefit certain patients, as currently used it subjects many patients, and society in general, to high costs and toxic effects. The study and editorial were published in the Feb. 2 Journal of the American Medical Association.