This 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 (mCRPC) who have previously received docetaxel.
This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1199 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 pre-specified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared to the placebo arm (HR=0.63 (95% CI: 0.53, 0.75), p < 0.0001). The median overall survival time was 18.4 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 to 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 enzalutamide administered orally once daily. Enzalutamide represents the third product that FDA has approved in the same disease setting within a period of 2 years.
Written by:
Ning YM, Pierce W, Maher VE, Karuri S, Tang S, Chiu HJ, Palmby T, Fourie Zirkelbach J, Marathe D, Mehrotra N, Liu Q, Ghosh D, Cottrell CL, Leighton J, Sridhara R, Ibrahim A, Justice R, Pazdur R. Are you the author?
DOP1/OHOP/CDER Food and Drug Administration.
Reference: Clin Cancer Res. 2013 Oct 18. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-13-1763
PubMed Abstract
PMID: 24141628
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