Session: MP29: Prostate Cancer: Advanced (including Drug Therapy) II
MP29-02: Efficacy and Safety of Darolutamide in Combination with Androgen-deprivation Therapy and Docetaxel in the North American Population from ARASENS
Introduction: In ARASENS (NCT02799602), darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced the risk of death by 32.5% (HR 0.68, 95% CI 0.57–0.80; P<0.0001) vs placebo (PBO) + ADT + docetaxel in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). DARO maintained quality of life, with similar control of disease-related physical symptoms and pain vs placebo, and had a favorable safety profile. We report clinical outcomes in North American (NA) pts in ARASENS. Methods: This international, double-blind, phase 3 trial randomized pts 1:1 to DARO 600 mg twice daily or PBO in addition to ADT + docetaxel. The primary endpoint was overall survival (OS). Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety. Results: Of 1305 pts analyzed, 244 (18.7%) were enrolled in North America (US/Canada 218/26; DARO/PBO 125/119) and of these, 36 (14.8%) were Black/African American (AA) pts. Baseline characteristics of the NA population were generally similar to those of the overall population, except for the proportion of pts with de novo metastatic disease (75.8% NA vs 86.1% overall). In NA pts, DARO + ADT + docetaxel was associated with OS benefit vs PBO + ADT + docetaxel (HR 0.59, 95% CI 0.39–0.89), with 4-year survival rates of 66% vs 50%, respectively. The DARO vs PBO group had longer time to CRPC (HR 0.32, 95% CI 0.21–0.48). The safety profile of DARO in NA pts was consistent with that of the overall population (grade 3/4 treatment-emergent adverse events [TEAEs] 61% NA vs 66% overall; serious TEAEs 44% NA vs 45% overall). The incidences of TEAEs associated with androgen receptor pathway inhibition for DARO vs PBO were generally consistent, particularly when adjusted for treatment exposure. The OS benefit and safety profile of DARO vs PBO was also seen in Black/AA pts, consistent with the overall population. Conclusions: In NA pts with mHSPC, addition of DARO to ADT + docetaxel led to a clinically meaningful reduction in risk of death by 41% and improved the key patient-relevant secondary endpoint of time to CRPC. Incidences of TEAEs were generally similar between treatment groups in NA pts and consistent with the overall population. SOURCE OF Funding: Bayer AG and Orion Pharma.
