The FDA has approved darolutamide for the treatment of patients with nonmetastatic castration-resistant prostate cancer.
The FDA has approved darolutamide (Nubeqa) for the treatment of patients with nonmetastatic castration-resistant prostate cancer.1
The approval of the androgen receptor inhibitor is based on data from the phase III ARAMIS trial, in which darolutamide in combination with androgen deprivation therapy (ADT) led to a 59% reduction in the risk of metastases or death compared with placebo/ADT in this patient population (HR, 0.41; 95% CI, 0.34-0.50; 2-sided, P <.0001).2,3 Moreover, the median metastasis-free survival (MFS) was 40.4 months with the addition of darolutamide versus 18.4 months with placebo/ADT at a median follow-up of 17.9 months.
The approval took place 3 months ahead of the agency's action date, stated Bayer, which jointly manufactures darolutamide with Orion Corporation, in a press release.
"Patients at this stage of prostate cancer typically don't have symptoms of the disease. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy," Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center, stated in the press release. "This approval marks an important new option for the prostate cancer community."
In the multicenter, double-blind, placebo-controlled, randomized phase III ARAMIS study, investigators evaluated the efficacy and safety of darolutamide in 1509 patients with nonmetastatic CRPC who were currently on standard ADT and at high risk for developing metastatic disease. Patients were randomized 2:1 to receive darolutamide at 600 mg twice daily plus ADT or placebo and ADT.
All patients had an ECOG performance status of 0 to 1. The primary endpoint was MFS, and key secondary endpoints were overall survival (OS), time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first symptomatic skeletal event, and characterization of the safety and tolerability.
OS data were not yet mature at the time of final MFS analysis, but data also showed a trend toward improved survival. The 3-year rates of OS were 83% in the darolutamide arm versus 73% with placebo, translating to a 29% reduction in the risk of death (HR, 0.71; 95% CI, 0.50-0.99, P = .0452), according to results of an interim analysis for OS.
Updated findings presented at the 2019 ASCO Annual Meeting showed that darolutamide also maintained quality of life and led to a delay in time to pain progression, which was defined as ≥2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in those treated with darolutamide compared with placebo.4 Pain progression was reported in 28% of all patients enrolled on the ARAMIS trial.
Regarding safety, both the darolutamide and placebo arms showed a 9% discontinuation rate due to adverse events (AEs). The most frequent AEs requiring discontinuation in patients who received darolutamide included cardiac failure (0.4%) and death (0.4%). AEs that occurred more frequently with darolutamide (≥2% over placebo) were fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% vs 1%).
"With the approval of Nubeqa, we now have a new therapy that extends MFS and allows physicians greater flexibility to treat men living with nmCRPC," Robert LaCaze, member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer, stated in the press release. "Bayer is proud to take this latest step forward in the nmCRPC treatment landscape. Nubeqa is the newest addition to our prostate cancer portfolio and reflects Bayer's commitment to finding treatments for men at different stages along the prostate cancer continuum."
In the press release, Bayer stated that it has also filed for approval for darolutamide in the European Union, Japan, and with other regulatory authorities.