title: U.S. Food and Drug Administration Approval Summary: Enzalutamide for the Treatment of Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.
abstract: The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60-0.84). The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14-0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30-0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide.
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA ningy@cder.fda.gov.
authors.forename: Yang-Min
authors.initials: YM
authors.lastname: Ning
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Brave
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: V Ellen
authors.initials: VE
authors.lastname: Maher
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kim
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
keywords: Androgen receptor inhibitor; Chemotherapy-naïve; Enzalutamide; Metastatic castration-resistant prostate cancer