THE INVESTIGATIONAL androgen receptor inhibitor darolutamide significantly improved metastasis-free survival in men with high-risk nonmetastatic castration-resistant prostate cancer vs placebo in the large phase III ARAMIS trial.1 Men treated with darolutamide had a median metastasis-free survival of 40.4 months vs 18 months for placebo (P < .001), representing a 59% improvement for metastasis or death. All secondary endpoints showed a benefit for darolutamide as well.
Karim Fizazi, MD, PhD, presents abstract 140 during an oral abstract session at the 2019 Genitourinary Cancers Symposium in San Francisco. Photo by © ASCO/Todd Buchanan 2019.
Darolutamide is a new entry to the androgen receptor inhibitor marketplace, with enzalutamide and apalutamide recently approved by the U.S. Food and Drug Administration for the treatment of nonmetastatic castration-resistant prostate cancer. Darolutamide is distinguished from its “cousins” because it does not cross the blood-brain barrier and therefore has less potential for central nervous side effects, such as seizures, falls, and cognitive impairment, and for drug-drug interactions than its predecessors.
“Darolutamide significantly improved metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Secondary and exploratory endpoints also support the benefit of darolutamide. Patients treated with darolutamide had delayed pain progression and similar quality of life compared with placebo. No clinically relevant differences in safety were seen between the two groups during the treatment period,” said lead author Karim Fizazi, MD, Institut Gustave Roussy, Université Paris-Sud, Villejuif, France.
“These results suggest that darolutamide should become a new standard of care for men with high-risk nonmetastatic castration-resistant prostate cancer,” he stated.
Results were published in The New England Journal of Medicine to coincide with Dr. Fizazi’s presentation at the 2019 Genitourinary Cancers Symposium.2 ■
DISCLOSURE: The trial was supported by Bayer Health Care and Orion Pharma. Dr. Fizazi is a consultant/advisor for Clovis Oncology, Roche/Genentech, ESSA, AstraZeneca, Curevac, Orion Pharma GmbH, Sano., Astellas Pharma, Bayer, Janssen Oncology; has received honoraria from Janssen, Sanofi, Astellas Pharma, Takeda, Merck, and Amgen; and travel/accommodations/expenses from Amgen.
1. Fizazi K, et al: ARAMIS: Efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC). 2019 Genitourinary Cancers Symposium. Abstract 140. Presented February 14, 2019.
2. Fizazi K, Shore N, Tammela TL, et al: Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. February 14, 2019 (early release online).
Ian Davis, MBBS (Hons), PhD, FRACP, FAChPM
THE FORMAL discussant of the ARAMIS trial, Ian Davis, MBBS (Hons), PhD, FRACP, FAChPM, of Monash University and Eastern Health, Melbourne, commented: “ARAMIS is a positive trial with encouraging early results. It has a meaningful endpoint of...