FDA Says Avastin Not Safe or Effective for Patients With Breast Cancer

After months of speculation, FDA Commissioner Margaret A. Hamburg, MD, has made a final decision regarding the use of Avastin (bevacizumab) to treat patients with breast cancer. On November 18, 2011, the commissioner announced that the FDA was withdrawing its approval of the drug to treat patients with breast cancer. The FDA stated that, after further review, it has determined that the drug is not safe or effective when it came to treating breast cancer.

“This was a difficult decision,” said Hamburg in a statement. “FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use.”

The decision comes after years of speculation about whether the drug actually helps patients. When Avastin was first approved for treating metastatic breast cancer patients in 2008, the approval was granted on the basis that further studies would be done. This approval went against the decision of the FDA’s Oncologic Drugs Advisory Committee (ODAC) and its decision to not recommend the drug for approval.

In July 2010, the ODAC again recommended against Avastin’s use in patients with advanced-stage breast cancer. Genentech, the company that manufactures Avastin, requested a hearing with the FDA that was granted in June 2011. The decision was upheld at that hearing to recommend against Avastin’s use in patients with breast cancer, but the final decision was made by Hamburg.

In August, after the hearing, Genentech put together a “middle-ground proposal” in which the drug would remain in the FDA’s accelerated approval program, suggesting revisions to the drug’s label for patients who had not received chemotherapy and whose tumors were characterized as aggressive hormone receptor (HR)-positive/HER2-negative or HR-negative/HER2-negative disease.

Safety and efficacy were addressed in numerous studies. In March, a meta-analysis of randomized controlled trials revealed treatment-related fatalities were 1.5 times higher for combination treatment with Avastin and chemotherapy versus chemotherapy alone. The review, which was published in the Journal of the American Medical Association, included 16 trials with 10,217 patients. Overall, treatment-related death occurred in 2.5% of the Avastin population.

In patients with breast cancer, studies failed to show statistically significant improvement in survival. In one example detailed in the FDA document, the AVF2119g study, an “open-label, multicenter, randomized trial evaluating Avastin in combination with capecitabine compared with capecitabine alone in 462 patients who had previously been treated with a taxane and anthracycline for breast cancer,” showed that there was no statistically significant difference in progression-free survival between the Avastin and capecitabine (4.9 months) arm and the capecitabine (4.2 months) arm (hazard ratio, 0.98; 95% confidence interval, 0.77-1.25; P = .86).

Before the FDA’s approval of Avastin was revoked by the FDA, many oncologists who treat patients with breast cancer felt that the drug did provide substantial benefits to certain patients, even in light of the ODAC’s recommendation against approval.

Joyce O’Shaughnessy, MD

“I believe Taxol/Avastin is an excellent treatment for patients with aggressive breast cancer,” said Joyce O’Shaughnessy, MD, co-director of breast cancer research at Baylor Charles A. Sammons Cancer Center in Dallas, Texas, in an interview at the 10th International Congress on The Future of Breast Cancer in California in August. “In the triple-negative subset of patients—many of whom are quite refractory to chemotherapy—where we have fewer options, I especially think that this is the area where Avastin fills its greatest unmet medical need.”

In the 69-page document outlining Hamburg’s decision as it was announced, the commissioner states the decision will not prevent Avastin from being prescribed to breast cancer patients. “[The] FDA does not regulate the practice of medicine, and it is part of the practice of medicine for a physician to be able to prescribe a drug that is approved for 1 use…for another, unapproved use,” Hamburg wrote in the document. Avastin remains approved by the FDA for treating patients with a number of other cancers, including colorectal, kidney, and lung cancers.

However, this change to Avastin’s status may affect coverage of the drug, which costs around $8,000 a month before insurance reimbursement is applied. In Hamburg’s document, she said that the Centers for Medicare & Medicaid Services plan to continue to reimburse patients on the drug. Other private insurance companies might be more reluctant, as FDA approvals do carry weight on whether or not certain drugs are covered.

Genentech said they are moving forward with a phase III study of Avastin in combination with paclitaxel in patients with untreated metastatic breast cancer that will utilize biomarkers to determine if certain patients will have better results with Avastin than others.

“We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment,” said Charlotte Arnold, a spokeswoman for Genentech, in a statement.