A subpopulation analysis of the Phase 3 ARASENS trial indicates that darolutamide, when combined with androgen deprivation therapy (ADT) and docetaxel, demonstrates significant efficacy and a manageable safety profile in Chinese patients with metastatic hormone-sensitive prostate cancer (mHSPC). The findings, presented at the 2023 ASCO annual meeting, suggest that the benefits observed in the global ARASENS trial extend to this specific demographic.
The ARASENS trial, a randomized, double-blind Phase 3 study, involved 1,305 patients with mHSPC who were randomized to receive either darolutamide 600 mg twice daily or placebo, in conjunction with ADT and docetaxel. The primary endpoint was overall survival (OS).
Key Findings in Chinese Subpopulation
In mainland China, 202 patients were included in the subpopulation analysis, with 104 receiving darolutamide and 98 receiving placebo. Baseline characteristics were generally well-balanced between the two groups, although the Chinese subpopulation exhibited a slightly higher proportion of patients with a Gleason score ≥8, a higher proportion with metastatic disease at diagnosis, and a higher median baseline PSA compared to the overall ARASENS population.
The analysis revealed a 36% reduction in the risk of death (HR 0.64, 95% CI 0.41–0.99) with darolutamide compared to placebo in Chinese patients. This result aligns with the 32.5% reduction observed in the overall ARASENS population (HR 0.68, 95% CI 0.57–0.80).
Secondary Endpoints
Key secondary endpoints also favored darolutamide. The time to castration-resistant prostate cancer was significantly longer in the darolutamide group (HR 0.32, 95% CI 0.20–0.50), as was the time to PSA progression (HR 0.22, 95% CI 0.13–0.37). Furthermore, 81% of patients in the darolutamide group experienced a maximum PSA decline of ≥90% from baseline at week 12, and 71% achieved a PSA level <0.2 ng/mL at any time.
Safety Profile
The incidence of treatment-emergent adverse events in Chinese patients was similar between the darolutamide and placebo groups, and comparable to the overall ARASENS population. The most common grade 3/4 treatment-emergent adverse event was neutropenia (darolutamide 64%, placebo 62%). Febrile neutropenia occurred in 4.0% of Chinese patients in the darolutamide group, compared to 7.6% in the overall population.
Clinical Implications
These findings support the use of darolutamide in combination with ADT and docetaxel for Chinese patients with mHSPC. The consistent efficacy and safety profile observed in this subpopulation reinforces the global ARASENS trial results and provides valuable insights for clinicians treating prostate cancer in China. According to Dr. Shanshan Wang, the results are consistent with the findings reported for the overall population in ARASENS.
