The androgen receptor (AR) antagonist darolutamide is generally well tolerated, helps patients maintain quality of life, and delays worsening of pain and disease-related symptoms in men with nonmetastatic castration-resistant prostate cancer (CRPC), according to an analysis of the ARAMIS trial.
The AR-targeted agents apalutamide and enzalutamide have demonstrated improvements in metastasis-free survival (MFS), but are also associated with increased rates of fatigue, falls, fractures, mental impairment, and other adverse events. “Because most men with nonmetastatic CRPC are asymptomatic, the major objective in these men is to prevent cancer progression while avoiding side effects,” said Karim Fizazi, MD, PhD, of the Institut Gustave-Roussy in France.
The ARAMIS trial previously showed that MFS was significantly improved with darolutamide compared with placebo. Fizazi presented results of an analysis on quality of life and related outcomes from the trial at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract 5000).
The study included 955 patients who received darolutamide and 554 patients who received placebo. The median age in both groups was 74 years, and other baseline characteristics were similar.
The time to pain progression was significantly extended with darolutamide, at a median of 40.3 months compared with 25.4 months with placebo, for a hazard ratio (HR) of 0.65 (95% CI, 0.53–0.79; P < .0001). The time to first symptomatic skeletal event was also extended; the median was not reached in either group, though the HR favored darolutamide, at 0.43 (95% CI, 0.22–0.84; P = .011).
Though it was considered an exploratory endpoint, Fizazi also noted that the time to deterioration on the Functional Assessment of Cancer Therapy-Prostate (FACT-P) subscale was improved with darolutamide, at 11.1 months compared with 7.9 months with placebo, for an HR of 0.80 (95% CI, 0.70–0.91; P = .0005).
“We are now showing that darolutamide delays worsening of pain and disease-related symptoms compared with placebo, and maintains quality of life,” Fizazi said. “This could make darolutamide an attractive treatment option for nonmetastatic CRPC.”
Daniel E. Spratt, MD, of the University of Michigan in Ann Arbor, was the discussant for the abstract. He said that the improvements in MFS and delayed prostate-specific antigen progression also represent improvements in quality of life, and longer follow-up will help confirm this. He noted, though, that the trial could not capture financial toxicity, which can be substantial.
Still, Spratt noted that the quality-of-life improvements were meaningful, and pointed out that sub-domain analyses showed improved outcomes in urinary and bowel symptoms with darolutamide, along with the skeletal outcomes and quality-of-life measures. “To me, this nominates darolutamide to be amongst the armamentarium of treating N0 CRPC, alongside apalutamide and enzalutamide,” he said.