Clinically relevant endpoints and quality-of-life outcomes with darolutamide in patients with metastatic hormone-sensitive prostate cancer: Analyses of the phase III ARASENS trial.

内容摘要

Patients with metastatic hormone-sensitive prostate cancer (mHSPC) require long-term treatment to delay progression and improve survival, while minimizing adverse events or negative impact on symptoms (e.g. pain) and health-related quality of life (HRQoL). In ARASENS (NCT02799602), darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (primary endpoint) versus placebo plus ADT and docetaxel. We report clinically relevant endpoints and HRQoL in ARASENS. Patients with mHSPC were randomized to darolutamide 600 mg orally twice daily or placebo, with ADT and docetaxel. Outcomes of interest were times to metastatic castration-resistant prostate cancer (mCRPC), pain progression, worsening of Brief Pain Inventory-Short Form pain interference/severity, and worsening of National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Prostate Cancer Symptom Index 17-item questionnaire (NFPSI-17) scores. In 1305 patients analyzed (darolutamide 651, placebo 654), darolutamide significantly delayed time to mCRPC (hazard ratio 0.36 [95 % confidence interval 0.30-0.42]) and time to pain progression (0.79 [0.66-0.95]) versus placebo. Times to worsening of pain interference/severity and NFPSI-17 scores were similar between treatment groups. Incidences of treatment-emergent adverse events (TEAEs) commonly associated with androgen receptor pathway inhibition were generally low and similar between groups (median follow-up: > 3.5 years). Darolutamide plus ADT and docetaxel provided significant benefits in clinically relevant endpoints versus ADT and docetaxel, with similar control of pain, maintenance of HRQoL, and no cumulative TEAEs over long-term treatment. These data reinforce darolutamide triplet therapy as a standard-of-care treatment option in patients with mHSPC.