FDA Grants Expanded Indication for Enzalutamide (Xtandi)

Megan Brooks

September 11, 2014

The US Food and Drug Administration (FDA) has approved the oral androgen receptor inhibitor enzalutamide (Xtandi, Astellas/Medivation) as first-line therapy for metastatic castration-resistant prostate cancer (CRPC), the manufacturers said in a joint news release issued September 10.

The FDA initially approved enzalutamide in August 2012 as second-line therapy in men with metastatic CRPC previously treated with docetaxel.

The new indication is for use in men with metastatic CRPC who have not received chemotherapy. It follows a priority review of the supplemental new drug application that was based on results of the phase 3 PREVAIL trial in men with CRPC and no previous chemotherapy.

In the trial, which was stopped early, men receiving enzalutamide and gonadotropin-releasing hormone therapy had a statistically significant improvement in overall survival and delayed time to radiographic progression or death compared with those receiving placebo and gonadotropin-releasing hormone therapy.

Compared with placebo, enzalutamide reduced the risk for death by 29% (hazard ratio [HR], 0.71; P < .0001) and the risk for radiographic progression or death by 83% (HR, 0.17; P < .0001). Treatment with enzalutamide also delayed time to initiation of chemotherapy and time to a skeletal related event.

In the setting of CRPC, "enzalutamide has been shown to extend overall survival and significantly delay the progression of prostate cancer," Tomasz M. Beer, MD, co-principal investigator of the PREVAIL study and deputy director of the Knight Cancer Institute and professor of medicine at Oregon Health & Science University in Portland, said in the news release.

"Furthermore, in the PREVAIL trial, the median time to initiating chemotherapy was delayed by 17 months with enzalutamide treatment as compared to placebo, so the result is a meaningful period of time during which men have their disease controlled without the need for chemotherapy," Dr. Tomasz noted.

In the PREVAIL trial and another phase 3 trial known as the Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy (AFFIRM), the most common adverse reactions (≥10%) that occurred more commonly (≥2% over placebo) in enzalutamide-treated patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo.

In clinical trials, seizures occurred in 0.9% of patients receiving enzalutamide who previously received docetaxel and 0.1% of patients who were chemotherapy-naive. "There is no clinical trial experience re-administering [enzalutamide] to patients who experienced a seizure, and limited clinical trial experience in patients with predisposing factors for seizure," the companies say.

Enzalutamide is not indicated for use in women.

Full prescribing information for enzalutamide is available on the drug Web site.


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