FDA Approves Enzalutamide for mCSPC Treatment

The FDA approved enzalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer.

The FDA approved a supplemental new drug application for enzalutamide (Xtandi) to treat men with metastatic castration-sensitive prostate cancer (mCSPC), according to Pfizer Inc. and Astellas Pharma Inc.

With this, enzalutamide the first and only oral treatment approved by the FDA in 3 distinct types of advanced prostate cancer: non-metastatic and metastatic castration-resistant prostate cancer (CRPC), and mCSPC. “This approval in metastatic castration-sensitive prostate cancer means physicians can now offer (enzalutamide) to men earlier in their advanced prostate cancer treatment journey,” Andrew Krivoshik, MD, PhD, senior vice president and oncology therapeutic area head at Astellas, said in a press release.

The agency based its approval on results from the randomized phase III ARCHES trial, designed to evaluate enzalutamide plus androgen deprivation therapy (ADT), compared with placebo and ADT, in 1,150 men with mCSPC. Across sites in the US, Canada, Europe, South America, and the Asia-Pacific region, patients were randomized to receive 160 mg daily enzalutamide or placebo and continued on a luteinizing hormone-releasing hormone agonist or antagonist or had a history of bilateral orchiectomy.

The trial achieved its primary endpoint of reducing radiographic progression-free survival (rPFS), defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation, with the addition of the agent to ADT demonstrating a 61% reduction, compared with placebo (hazard ratio [HR], 0.39; 95% CI, 0.30-0.50; P <.0001). Of note, radiographic disease progression was defined by the identification of 2 or more new bone lesions on a bone scan with confirmation per the Prostate Cancer Working Group 2 criteria, and/or progression in soft tissue disease.

At the time of final rPFS analysis, overall survival data were not mature.

“Men with metastatic castration-sensitive prostate cancer face complex treatment decisions and it is critical for physicians and patients to have as much information as possible when deciding on all of the options available,” lead investigator Andrew Armstrong, MD, professor of medicine, surgery, pharmacology and cancer biology, and director of research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers, said in the release. “The research supporting the FDA approval and updated treatment guidelines provide physicians and patients with compelling evidence to consider enzalutamide as a treatment option for men with this disease.”

The companies noted that the safety analysis appeared consistent with that previously seen. The common adverse events (AEs) in the enzalutamide and placebo arms included hot flush (27.0% vs 22.0%, respectively), asthenic conditions (24.0% vs 20.0%), hypertension (8.0% vs 5.6%), fractures (6.5% vs 4.2%), and musculoskeletal pain (6.3% vs 4.0%). 

“(This) approval adds to over a decade of global clinical research aimed at better understanding the potential benefit of (enzalutamide) for men with advanced prostate cancer,” Andy Schmeltz, global president of Pfizer Oncology, said in the release. “The FDA approval marks continued progress to help meet the needs of patients, including men living with metastatic castration-sensitive prostate cancer.”



Xtandi (Enzalutamide) approved by U.S. FDA for the treatment of metastatic castration-sensitive prostate cancer [news release]. Pfizer. Published December 16, 2019. https://bit.ly/2tpujIV. Accessed December 16, 2019.