FDA Approves Enzalutamide (Xtandi) for Late-Stage Prostate Cancer

The US Food and Drug Administration (FDA) approved enzalutamide (Xtandi), a once-daily oral therapy for men with metastatic castration-resistant prostate cancer that has either spread to other organs or recurred, despite prior surgical or medical treatment. The drug, originally known as MDV3100, is now part of a growing number of therapies for late-stage prostate cancer.

Enzalutamide is approved for prostate cancer for patients previously treated with docetaxel and was reviewed as part of a 6-month expedited review. The accelerated review is for therapies that could offer a treatment for diseases where no appropriate options are available. In the case of enzalutamide, the FDA announced the approval after only a 3-month review period, well ahead of the prescription drug user fee goal date of November 22, 2012. Enzalutamide is a second-generation androgen receptor inhibitor that targets the main driver of prostate growth-the multi-step androgen-signaling pathway.

“The need for additional treatment options for advanced prostate cancer continues to be important for patients,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research in a press release. “Xtandi is the latest treatment for this disease to demonstrate its ability to extend a patient’s life.”

The overall survival results of the 1,199 patient phase III AFFIRM trial were recently published in the New England Journal of Medicine. Enzalutamide increased survival of patients by almost 5 months, from 13.6 months for those patients receiving placebo compared to 18.4 months for those in the experimental arm (P < .001). All patients had previously been treated with docetaxel.

The most common side effects of the drug are weakness, back pain, diarrhea, joint pain, among others. One concerning side effect is seizures, which occur in approximately 1% of patients. The AFFIRM trial had excluded patients with a history of seizure and brain injuries. Therefore, the safety of enzalutamide in these patients is not known.

Prior to 2004, men with castration-resistant prostate cancer were predominantly treated with docetaxel, a chemotherapy. Since then, enzalutamide is joining three new therapies that are already on the market-cabazitaxel (Jevtana), the immunotherapy sipuleucel-T (Provenge), and the oral therapy abiraterone acetate (Zytiga).

Enzalutamide is also being investigated for treatment of men with late-stage prostate cancer who have failed androgen deprivation therapy but have not been previously treated with chemotherapy.  The placebo-controlled international trial is evaluating the overall survival of patients and is expected to accrue about 1,680 patients.

Enzalutamide was developed by the San Francisco-based Medivation along with Japan-based Astellas Pharma.