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Darolutamide added to androgen deprivation therapy for nonmetastatic castration-resistant prostate cancer: overall survival results of phase III ARAMIS study

Darolutamide ( Nubeqa ) is a structurally distinct androgen receptor inhibitor with a favorable safety profile, approved for treating men with nonmetastatic castration-resistant prostate cancer ( nmCRPC ) after demonstrating significantly prolonged metastasis-free survival, compared with placebo, in the phase III ARAMIS trial: median 40.4 vs 18.4 months, respectively ( hazard ratio, HR=0.41; 95% CI 0.34–0.50; P less than 0.0001 ).

Researchers have reported final analyses of overall survival ( OS ) and prospectively collected, patient-relevant secondary endpoints, and updated safety results.

1509 patients with nonmetastatic castration-resistant prostate cancer were randomized 2:1 to Darolutamide 600 mg twice daily ( n=955 ) or placebo ( n=554 ) while continuing androgen deprivation therapy ( ADT ).
Secondary endpoints included overall survival, and times to pain progression, first cytotoxic chemotherapy, and first symptomatic skeletal event.
The overall survival analysis was planned to occur after approximately 240 deaths.

Final analysis was conducted after 254 deaths were observed ( 15.5% of Darolutamide and 19.1% of placebo patients ).
After unblinding at the primary analysis, 170 patients crossed over from placebo to Darolutamide.
Darolutamide has shown a statistically significant overall survival benefit corresponding to a 31% reduction in the risk of death compared with placebo.
All other secondary endpoints were significantly prolonged by Darolutamide, regardless of the effect of crossover and subsequent therapies on survival benefit.

Incidences of treatment-emergent adverse events with greater than or equal to 5% frequency were generally comparable between Darolutamide and placebo, similar to the safety profile observed at the primary analysis.
Incidences of adverse effects of interest ( including falls, CNS effects, and hypertension ) were not increased with Darolutamide compared with placebo when adjusted for treatment exposure.
Adverse effects in the crossover group were consistent with those for the Darolutamide treatment arm.

In conclusion, Darolutamide has shown a statistically significant overall survival benefit for men with nonmetastatic castration-resistant prostate cancer. In addition, Darolutamide delayed onset of cancer-related symptoms and subsequent chemotherapy, compared with placebo.
With extended follow-up, safety and tolerability were favorable and consistent with the primary ARAMIS analysis ( Fizazi et al, N Engl J Med 2019 ). ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020