• Yangmin M Ning, William Pierce, V Ellen Maher, Stella Karuri, Sheng-Hui Tang, Haw-Jyh Chiu, Todd Palmby, Jeanne Fourie Zirkelbach, Dhananjay Marathe, Nitin Mehrotra, Qi Liu, Debasis Ghosh, Christy L Cottrell, John Leighton, Rajeshwari Sridhara, Amna Ibrahim, Robert Justice, and Richard Pazdur.
• Authors' Affiliations: Office of Hematology and Oncology Products, Office of New Drugs, Office of Biostatistics, Office of Clinical Pharmacology, Office of New Drug Quality Assessment, and Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
• Clin Cancer Res. 2013 Nov 15;19(22):6067-73.

AbstractThis article summarizes the regulatory evaluation that led to the full approval of enzalutamide (XTANDI, Medivation Inc.) by the U.S. Food and Drug Administration (FDA) on August 31, 2012, for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1,199 patients with mCRPC who had received prior docetaxel to receive either enzalutamide, 160 mg orally once daily (n = 800), or placebo (n = 399). All patients were required to continue androgen deprivation therapy. The primary endpoint was overall survival. At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared with the placebo arm [HR = 0.63; 95% confidence interval: 0.53-0.75; P < 0.0001]. The median overall survival durations were 18.4 months and 13.6 months in the enzalutamide and placebo arms, respectively. The most common adverse reactions (≥10%) included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, and upper respiratory infection. Seizures occurred in 0.9% of patients on enzalutamide compared with no patients on the placebo arm. Overall, the FDA's review and analyses of the submitted data confirmed that enzalutamide had a favorable benefit-risk profile in the study patient population, thus supporting its use for the approved indication. The recommended dose is 160 mg of enzalutamide administered orally once daily. Enzalutamide represents the third product that the FDA has approved in the same disease setting within a period of 2 years. Clin Cancer Res; 19(22); 6067-73. ©2013 AACR.

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