LBA01-07: Overall Safety and Incidences of Adverse Events by Time Interval With Darolutamide Plus Androgen-deprivation Therapy and Docetaxel in the Phase 3 ARASENS Trial

E. David Crawford, Matthew R. Smith, Bertrand Tombal, Karim Fizazi, Maha Hussain, Cora N. Sternberg, Arash Rezazadeh Kalebasty, Ronald Tutrone, Neal D. Shore, Laurence Belkoff, Silke Thiele, Rui Li, Iris Kuss, Heikki Joensuu, Fred Saad

Introduction: In ARASENS, darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced risk of death by 32.5% (hazard ratio [HR] 0.675; 95% confidence interval [CI] 0.568–0.801; P<0.0001) vs ADT + docetaxel in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). We report adverse events (AEs) and their incidences by time interval from ARASENS (NCT02799602).

Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or matching placebo (PBO) + ADT + docetaxel. AE incidences by time interval were defined as number of pts with new-onset AE or worsening AE in an interval (every 3 months for year 1; 6 months for year 2) divided by number of pts in that interval. For AEs associated with AR pathway inhibitors, exposure-adjusted incidence rates (EAIR) are presented per 100 pt years to adjust for differences in treatment duration between groups.

Results: Of 1306 pts randomized, safety was evaluated in 1302 pts who received DARO (652) or PBO (650). Incidences of any-grade AEs (99.5%; 98.9%), grade 3–5 AEs (70.2%; 67.5%), serious AEs (44.8%; 42.3%), and discontinuations of DARO/PBO due to AEs (13.5%; 10.6%) were comparable for both groups. The most frequently reported AEs were alopecia (40.5%; 40.6%), neutropenia (39.3%; 38.8%), and fatigue (33.1%; 32.9%); incidences in both groups were highest in the first 6 months of treatment during the docetaxel treatment period and progressively decreased thereafter (Table). Similar trends were observed for other AEs reported in >10% of pts in either treatment group, including peripheral edema, diarrhea, nausea, increased serum liver enzyme concentrations, and peripheral neuropathy. Most AEs associated with AR pathway inhibitors showed =2% difference between DARO and PBO. Rash (16.6%; 13.5%) and hypertension (13.7%; 9.2%) (both grouped preferred terms) occurred in more pts receiving DARO vs PBO, but EAIRs were similar between groups (rash: 6.2; 7.3; hypertension: 5.1; 5.0).

Conclusions: DARO + ADT + docetaxel significantly increased overall survival without added toxicity. In general, AE incidence was similar in both groups, with the highest incidence during the first 6 months of overlapping docetaxel treatment.

Source of Funding: Bayer AG and Orion Pharma