Avastin in Combination With Chemo Associated With Increased Fatality

A team of researchers at Stony Brook University School of Medicine in New York published a paper in JAMA last week showing that patients who receive Avastin (bevacizumab), in combination with chemotherapy are at increased risk of side effects that may lead to death. Lead author Dr. Vishal Ranpura and his colleagues reported that the risk of fatal adverse events varied according to the type of chemotherapy agents used in conjunction with Avastin. There were also suggestions that the risk might vary by tumor type and dose of Avastin, but results were not definitive.

The randomized trials reviewed in this analysis involved more than 10,200 patients. Overall fatal events in patients who received Avastin was low--2.5% compared to 1.7 percent of patients who did not receive it. However, the increased risk was more than three times higher in patients who received Avastin in combination with platinum or taxane chemotherapy agents such as carboplatin and paclitaxel. The most common fatal event, accounting for nearly one-quarter of the total, was hemorrhage. 

This finding will most likely affect overall usage of Avastin. Because the most significant benefits from Avastin are seen, thus far, in colorectal cancer, it may be that the drug is used with less frequency for treating lung or breast cancers, where the risk may not outweigh the benefits.

In an editorial accompanying the new article in JAMA, Dr. Daniel Hayes of the UMichigan Comprehensive Cancer Center remarked that treatment with Avastin can run as high as $100,000 a year, but it is still unclear which patients benefit most from the drug. In fact, improvements in only three of the trials upon which FDA approval for Avastin were based, overall survival increased by less than three months. 

Genentech, the makers of Avastin, recently issued a response to the article that includes the following statement:

"...this meta-analysis includes cancer types for which Avastin is not approved by the US Food and Drug Administration (FDA) and should not be used, including advanced squamous* cell non–small-cell lung cancer (NSCLC), advanced prostate cancer and advanced pancreatic cancer. (Avastin is approved for advanced non-squamous NSCLC in combination with carboplatin and paclitaxel chemotherapy.)

For three of the FDA-approved cancer types (advanced colorectal, renal cell and breast cancers), the incidence of treatment-related deaths reported in this analysis was similar between the Avastin and the control groups.  The higher incidence in NSCLC is known, however, the incidence reported in this analysis is greater than previously reported due to the fact that the analysis included patients with advanced squamous cell NSCLC, for which Avastin is not indicated. Overall, the authors note that “the absolute risk of treatment-related mortality is low” and the data should be considered in the context of potential benefit with Avastin."

For the full JAMA article, go here.