The Avastin Uproar
Some of you have likely been following the uproar over Avastin's value as a treatment for breast cancer. Particularly for women with Stage IV cancer, this has been a riveting issue with passionate feelings on both sides. Here is a good summary from Journal Watch:
Bevacizumab for Breast Cancer: Benefit vs. Risk
The addition of bevacizumab to other regimens was associated with excess risk for fatal adverse events.
The promise of antiangiogenic therapy seemed to be realized with the approval of bevacizumab in combination with chemotherapy for treatment of patients with colorectal cancer, non-small-cell lung cancer, breast cancer, renal cancer, or glioblastoma multiforme. However, the true impact of bevacizumab on patient outcomes is debated, not only because of its variable efficacy and high monetary cost, but also because of the uncommon fatal adverse events (FAEs) that have been attributed to the drug. Thus, the FDA recently recommended rescinding approval of bevacizumab for treating patients with breast cancer because of a lack of survival benefit as well as concern about rare, fatal adverse events. To get a better overall sense of bevacizumab-related fatalities, investigators performed a review and meta-analysis of 16 randomized controlled trials involving >10,000 patients with a variety of advanced malignancies.
Overall incidence of FAEs with bevacizumab was 2.5%. Compared with chemotherapy alone (FAE incidence, 1.7%), addition of bevacizumab was associated with excess risk for FAEs (relative risk, 1.46). Analysis that took bevacizumab dose into account (high dose: 5 mg/kg/week; low dose: 2.5 mg/kg/week) showed that, although FAEs were more common with high-dose bevacizumab, the difference was not significant. Bevacizumab was associated with excess risk for FAEs in patients who received platinum- and taxane-based regimens (RR, 3.49) but not other agents.
Incidence of FAEs did not vary across tumor types. The most common FAEs were hemorrhage (23.5%), neutropenia (12.2%), and gastrointestinal perforation (7.1%).
The value of any cancer therapy is determined by its benefits weighed against its adverse event profile. Risk for fatal adverse events must be considered carefully, particularly if no improvement in overall survival can be expected. Although this analysis puts into perspective FAEs secondary to bevacizumab use across tumor types, decisions about incorporating bevacizumab into therapy must be individualized. Ultimately, clinicians must be aware of the potential for catastrophic adverse events associated with bevacizumab use and must exercise clinical judgment accordingly.
— William J. Gradishar, MD
Published in Journal Watch Oncology and Hematology
March 8, 2011
Ranpura V et al. Treatment-related mortality with bevacizumab in cancer patients: A meta-analysis.
JAMA 2011 Feb 2; 305:487.
Hayes DF. Bevacizumab treatment for solid tumors: Boon or bust?
JAMA 2011 Feb 3; 305:506.