FDA Updates: Pertuzumab Moves Forward, Denosumab Receives Setback

While pertuzumab is moving ahead in the FDA approval process, an additional indication for denosumab might be halted.

The FDA has committed a breast cancer drug to accelerated review, while an advisory panel has recommended against adding a new indication to treat prostate cancer for a bone metastases drug, since it failed to provide meaningful benefit to patients.

The FDA announced that the breast cancer drug pertuzumab would receive a priority review, meaning that the agency will make a decision about approving the drug by June 8, 2012.

Pertuzumab is a humanized monoclonal antibody that is being studied in early and advanced HER2-positive breast cancer and advanced HER2-positive gastric cancer. Genentech, a member of the Roche group, is seeking approval of the drug for use with trastuzumab and docetaxel in previously untreated patients with HER2-positive metastatic or locally recurrent, unresectable breast cancer, as well as patients who have relapsed after receiving adjuvant therapy.

The FDA approved the priority review based on the results of the phase III CLEOPATRA study, which was published in The New England Journal of Medicine in January. The study randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive either pertuzumab plus trastuzumab and docetaxel or a placebo plus trastuzumab and docetaxel. The median progression-free survival in the pertuzumab group was 18.5 months compared to 12.4 months in the control group (hazard ratio [HR] for death or progression, 0.62; 95% CI, 0.51 to 0.75; P< .001). Complete overall survival results were not available at the time of publication, but there was a strong trend in favor of the pertuzumab group.

“We are pleased that the FDA has granted pertuzumab a priority review because new medicines are needed for HER2-positive breast cancer,” said Hal Barron, MD, chief medical officer and head of Global Product Development at Genentech, in a statement released on Tuesday. “We have been researching HER2-positive breast cancer for more than 30 years, and we hope an expedited review will help us quickly bring another personalized medicine to people battling this aggressive disease.”

While pertuzumab is moving ahead in the FDA approval process, an additional indication for denosumab (Xgeva) might be halted. The FDA’s Oncologic Drugs Advisory Committee voted 12 to 1 that the benefits of using the drug to prevent bone metastases in men who are not responsive to hormone treatment and have recurring prostate cancer did not outweigh the risks.

The FDA approved Xgeva, manufactured by Amgen, to prevent bone pain and fractures in patients with bone metastases in November 2010. Amgen investigated the efficacy of the drug in patients with advanced-stage prostate cancer, since an estimated 90% of cases of advanced disease metastasize to the bones. The company sought this second approval after a phase III trial in men with high-risk non-metastatic castration-resistant prostate cancer showed that bone metastasis-free survival increased by a median of 4.2 months in patients who received denosumab compared to a placebo (HR 0.85, CI 0.73 to 0.98; P =.028). However, the study did not show any significant difference in overall survival benefit between the 2 groups, and patients taking denosumab were at higher risk for osteonecrosis of the jaw. This condition occurred in 4.6% of patients in the denosumab group but none of the patients in the control group.

The FDA is scheduled make a decision on whether to approve Xgeva for this indication by April 26, 2012.