Darolutamide shows ‘high efficacy’ for nonmetastatic prostate cancer
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Darolutamide conferred higher rates of 3-year OS than placebo among men with nonmetastatic castration-resistant prostate cancer, according to the final analysis of the ARAMIS trial published in The New England Journal of Medicine.
Darolutamide (Nubeqa, Bayer), an androgen receptor inhibitor, also prolonged time to pain progression, time to first use of cytotoxic chemotherapy and time to first symptomatic skeletal event.
“When we initiated the ARAMIS trial, there was no standard of care for men with nonmetastatic castrate-resistant prostate cancer — men and physicians were simply watching PSA rising and treatment could be started only when the imaging showed evidence of metastases,” Karim Fizazi, MD, PhD, head of the department of cancer medicine at Institut Gustave Roussy in Villejuif, France, and professor in oncology at University of Paris, told Healio. “The high efficacy and the excellent safety profile observed in the phase 1 to phase 3 program that we conducted made it a perfect candidate to improve outcomes among patients with nonmetastatic castrate-resistant prostate cancer while maintaining their quality of life.”
The planned primary analysis of the double-blind, phase 3 ARAMIS trial — which randomly assigned 1,509 men (median age, 74 years) 2:1 to 600 mg twice-daily darolutamide (n = 955) or placebo (n = 554) while continuing to receive androgen deprivation therapy — showed a 59% reduction in the risk for metastases.
This finding led to unmasking of the treatment groups, and patients in the placebo group were permitted to crossover to treatment with darolutamide. At that time, all 170 patients still receiving placebo crossed over; the 137 patients who discontinued placebo before unmasking received at least one other life-prolonging therapy.
For the prespecified final analysis, investigators evaluated OS and other secondary endpoints — including time to pain progression, time to first use of cytotoxic chemotherapy and time to first symptomatic skeletal event — after 254 deaths occurred (148 in the darolutamide arm vs. 106 in the placebo arm).
Overall median follow-up was 29 months, representing 11.2 additional months after the primary analysis of metastasis-free survival.
Results showed a 3-year OS benefit of 83% (95% CI, 80-86) with darolutamide vs. 77% (95% CI, 72-81) with placebo. Darolutamide conferred a 31% reduction in the risk for death (HR = 0.69; 95% CI, 0.53-0.88).
Researchers reported a significant benefit with darolutamide for median time to pain progression (40.3 months vs. 25.4 months; HR = 0.65; 95% CI, 0.53-0.79). Also, at 3 years, a greater proportion of men treated with darolutamide did not experience a first symptomatic skeletal event (96% vs. 92%; HR = 0.48; 95% CI, 0.29-0.82) and did not receive their first cytotoxic chemotherapy (83% vs. 75%; HR = 0.58; 95% CI, 0.44-0.76).
Adverse events occurred among 85.7% of men who received darolutamide and among 79.2% of men who received placebo during the masked study protocol, followed by 70% among those who crossed over during the open-label period. Researchers reported no new safety signals.
As Healio previously reported, these data led to the FDA approval of darolutamide for this patient population in July.
“Our findings showed that men with high-risk nonmetastatic castrate-resistant prostate cancer should be treated early with an androgen receptor inhibitor,” Fizazi said. “When choosing the best treatment for a patient, the side effect profile of drugs should be carefully considered and discussed with the patient. Darolutamide is not associated with adverse events typically seen with other androgen receptor inhibitors or to a much lesser degree.
“Future research should focus on how we transfer the knowledge from ARAMIS and improve and optimize patient treatment in other prostate disease states with darolutamide, such as men with high-risk localized disease or those with metastases,” he said.
For more information:
Karim Fizazi, MD, PhD, can be reached at the Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France; email: karim.fizazi@gustaveroussy.fr.
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