Bevacizumab for glioblastoma and advanced cervical cancer
April 1, 2014
Bevacizumab (Avastin) is Genentech’s blockbuster angiogenesis inhibitor that works by slowing the growth of new blood vessels. The drug is used to treat several types of cancer and is used off label to treat macular degeneration. Bevacizumab has mostly been used to treat recurrent and metastatic cancers such as glioblastoma, but more recently has become standard initial therapy for certain solid tumors such as colon and lung cancer. It was briefly approved for the treatment of breast cancer, but that indication was revoked by the FDA in late 2011. Now, bevacizumab is being looked at for initial treatment of glioblastoma, the most common primary malignant brain tumor, and advanced cervical cancer.
Unfortunately, bevacizumab failed to improve survival in patients with newly diagnosed glioblastoma in two new studies. In the first study, 637 patients with glioblastoma were randomized to standard treatment with temozolomide/radiation therapy along with either bevacizumab or placebo starting at week 4. There was no significant difference in the duration of overall survival (15.7 months with drug vs 16.1 months with placebo). Progression-free survival was prolonged with bevacizumab (10.7 vs 7.3 months), but side effects were more common with the drug, including hypertension, thromboemobolic events, intestinal perforation, and neutropenia. Quality-of-life measures and neurocognition also declined more frequently with bevacizumab. In the second similarly designed study, newly diagnosed patients were also treated with temozolomide/radiation and were randomized to bevacizumab or placebo every 2 weeks for 6 weeks, then maintenance doses of temozolomide and bevacizumab or placebo. More than 450 patients were randomized to each group. Median progression-free survival was longer in the bevacizumab group (10.6 months vs 6.2 months) but overall survival did not differ significantly with overall survival for bevacizumab vs placebo, respectively, 72.4% vs 66.3% at 1 year, and 33.0% vs 30.1% at 2 years (P = 0.24). More adverse effects were seen in the bevacizumab treatment arm. These studies suggest that the addition of bevacizumab to standard therapy with temozolomide/radiation does not improve survival in patients with glioblastoma but may improve progression-free survival, but with the possibility of higher rates of significant side effects, including neurocognitive decline (N Engl J Med2014;370:699-708, 709-722).
In the same issue of the New England Journal of Medicine, a new study showed that bevacizumab is effective for prolonging survival in women with advanced cervical cancer. More than 450 women with previously treated recurrent disease were randomized to chemotherapy with or without bevacizumab until disease progression, the development of unacceptable side effects, or complete response was documented. The bevacizumab-containing combination chemotherapies were associated with increased overall survival (17.0 months vs 13.3 months; hazard ratio, 0.71; 98% confidence interval, 0.54-0.95; P = 0.004) as well as a higher response rate. The drug caused more adverse reactions, including hypertension, thromboembolic events, and gastrointestinal fistulas. The authors conclude that addition of bevacizumab to combination chemotherapy in women with advanced cervical cancer improved median overall survival by 3.7 months (N Engl J Med2014;370:734-743).
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