METASTATIC hormone-sensitive prostate cancer (mHSPC) often begins asymptomatically but typically progresses to metastatic castration-resistant prostate cancer (CRPC) within 1–3 years on androgen-deprivation therapy (ADT) alone. This progression is linked to reduced survival and a poorer quality of life, underscoring the need for early, effective treatments.
Recent years have seen the international standard of care for mHSPC evolve to include ADT combined with docetaxel or androgen receptor pathway inhibitors (ARPI) such as abiraterone acetate, enzalutamide, or apalutamide. Clinical trials, including the ARASENS and PEACE-1 studies, have highlighted the significant survival benefits of these combinations. Darolutamide, a distinct and potent androgen receptor inhibitor with minimal drug interactions, emerged as a key player in the ARASENS study. Its addition to ADT and docetaxel reduced the risk of death by 32.5% compared to placebo, offering benefits across various risk profiles.
In Japanese patients, who constituted 11.3% of the ARASENS population, darolutamide showed promising outcomes. Despite the subgroup being older and presenting higher-risk disease features, darolutamide prolonged the time to CRPC and improved survival trends. Importantly, Japanese patients tolerated the regimen well, with most completing the full course of docetaxel and maintaining long-term darolutamide treatment.
Adverse events (AEs) such as febrile neutropenia and neutropenia, known to be associated with docetaxel, were slightly more frequent in Japanese patients, reflecting previously observed ethnic differences. Cardiac disorders and falls were more common in the darolutamide group, possibly due to the older age of these patients and the longer treatment duration. Proactive management and patient education on these potential AEs are recommended, especially during the initial six months of therapy.
While the study was not powered for subgroup analysis, the findings align with those of the overall population, supporting darolutamide’s integration into treatment protocols for mHSPC in Japanese patients. This combination represents a promising new standard of care, with the potential to significantly delay disease progression and improve survival.
Katie Wright, EMJ
Reference
Uemura M et al. Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis. Cancer Med. 2024;13(21):e70029.
