As reported in the Journal of Clinical Oncology by Andrew J. Armstrong, MD, ScM, and colleagues, the final overall survival analysis of the phase III ARCHES trial showed a significant benefit with the addition of enzalutamide to androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer.
The trial supported the December 2019 approval of enzalutamide plus ADT in this setting on the basis of improved radiographic progression–free survival.
Study Details
In the international double-blind trial, 1,150 patients were randomly assigned between March 2016 and January 2018 to receive enzalutamide at 160 mg once daily plus ADT (n = 574) or placebo plus ADT (n = 576). The primary endpoint was radiographic progression–free survival; overall survival was a key secondary endpoint. The data cutoff for the final overall survival analysis was in May 2021.
In ARCHES, enzalutamide plus ADT significantly reduced the risk of death in patients with metastatic hormone-sensitive prostate cancer by 34% vs placebo plus ADT. The survival benefit of enzalutamide plus ADT became more apparent with additional follow-up.— Andrew J. Armstrong, MD, ScM, and colleagues
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Key Findings
Median follow-up was 44.6 months.
After study unblinding, a total of 180 (31.3%) progression-free patients in the control group crossed over to receive open-label enzalutamide plus ADT. A total of 23% of the enzalutamide group and 38% of the control group received subsequent life-prolonging therapy; 8% of patients in the crossover group received life-prolonging therapy after discontinuing enzalutamide plus ADT. Including crossover, 70% of the control group received subsequent therapy, with enzalutamide as first treatment in 42%.
Overall survival was significantly improved in the enzalutamide group, with a hazard ratio (HR) of 0.66 (95% confidence interval [CI] = 0.53–0.81, P < .001). Median overall survival was not reached in either group. Overall survival at 24, 36, and 48 months was 86% vs 82%, 78% vs 69%, and 71% vs 57%. A prespecified rank-preserving structural failure time sensitivity analysis to adjust for potential crossover effect showed a hazard ratio of 0.57 (95% CI = 0.45–0.70, P < .001), with a median overall survival of not reached vs 47.7 months.
At the time of the current analysis, median radiographic progression–free survival was 49.8 months (95% CI = 47.3 months–not estimable) vs 38.9 months (95% CI = 28.2–46.2 months; HR = 0.63, 95% CI = 0.52–0.76). Median time to next subsequent antineoplastic therapy was not reached (95% CI = not estimable–not estimable) vs 40.5 months (95% CI = 26.3 months–not estimable; HR = 0.38, 95% CI = 0.31–0.48).
The investigators concluded, “In ARCHES, enzalutamide plus ADT significantly reduced the risk of death in patients with metastatic hormone-sensitive prostate cancer by 34% vs placebo plus ADT. The survival benefit of enzalutamide plus ADT became more apparent with additional follow-up.”
Dr. Armstrong, of the Duke Cancer Institute Center for Prostate & Urologic Cancers, Duke University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Astellas Pharma Inc and Pfizer Inc. For full disclosures of the study authors, visit ascopubs.org.
