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FDA Approval for Enzalutamide

Brand name(s): Xtandi®

  • Approved for metastatic castration-resistant prostate cancer following docetaxel therapy.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications.

On August 31, 2012, the Food and Drug Administration (FDA) approved enzalutamide (Xtandi® Capsules, made by Medivation, Inc., and Astellas Pharma US, Inc.), for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. 

The approval was based on a single randomized placebo-controlled multicenter trial that enrolled 1199 patients with metastatic castration-resistant prostate cancer who had received prior docetaxel. Patients were randomly assigned to receive enzalutamide 160 mg orally once daily (N = 800) or placebo (N = 399). Study treatment continued until disease progression, initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal. Patients were required to continue androgen deprivation therapy and were allowed, but not required, to continue or initiate glucocorticoids during the study period. Forty-eight percent of patients in the enzalutamide group and 46 percent of those in the placebo group received glucocorticoids. 

The primary efficacy endpoint was overall survival (OS). At the pre-specified interim analysis after 520 events, a statistically significant improvement in OS [HR 0.63 (95 percent CI: 0.53, 0.75), p < 0.0001, log rank test] was observed in patients in the enzalutamide group compared with patients in the placebo group[RC1] . The median OS was 18.4 months for patients who received enzalutamide and 13.6 months for patients who received placebo.

The most common (at least 5 percent) grade 1-4 adverse reactions included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Grade 3-4 adverse reactions were reported in 47 percent of patients treated with enzalutamide and in 53 percent of those who received placebo.

Seizures occurred in 0.9 percent of patients treated with enzalutamide. No patients in the placebo group experienced seizures. In the clinical trial, patients who experienced a seizure were permanently discontinued from therapy. All seizures resolved. Patients with a history of seizure, who were taking medications known to decrease the seizure threshold, or who had other risk factors for seizures were excluded from the clinical trial. The safety of enzalutamide in patients with predisposing factors for seizures is unknown. 

The recommended dose and schedule for enzalutamide is 160 mg orally once daily.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

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  • Updated: July 3, 2013