title: Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary.
abstract: 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 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.
authors.affiliation: 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.
authors.forename: Yangmin M
authors.initials: YM
authors.lastname: Ning
authors.forename: William
authors.initials: W
authors.lastname: Pierce
authors.forename: V Ellen
authors.initials: VE
authors.lastname: Maher
authors.forename: Stella
authors.initials: S
authors.lastname: Karuri
authors.forename: Sheng-Hui
authors.initials: SH
authors.lastname: Tang
authors.forename: Haw-Jyh
authors.initials: HJ
authors.lastname: Chiu
authors.forename: Todd
authors.initials: T
authors.lastname: Palmby
authors.forename: Jeanne Fourie
authors.initials: JF
authors.lastname: Zirkelbach
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Marathe
authors.forename: Nitin
authors.initials: N
authors.lastname: Mehrotra
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Debasis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Christy L
authors.initials: CL
authors.lastname: Cottrell
authors.forename: John
authors.initials: J
authors.lastname: Leighton
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D000077143:Docetaxel; D017277:Drug Approval; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality*; D013534:Survival; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide