No published head-to-head randomized trials have compared the safety and efficacy of darolutamide versus apalutamide or enzalutamide in nonmetastatic castration-resistant prostate cancer. This study compares pre-specified adverse events and metastasis-free survival associated with darolutamide vs apalutamide, and darolutamide vs enzalutamide, via matching-adjusted indirect comparisons.
Individual patient data from the phase III ARAMIS trial (NPLACEBO=553; NDAROLUTAMIDE=943) were selected and re-weighted to match the inclusion criteria and baseline characteristics published for the phase III SPARTAN (NPLACEBO=401; NAPALUTAMIDE=806) and PROSPER (NPLACEBO=468; NENZALUTAMIDE=933) trials. Only baseline factors consistently reported across trials were included as matching covariates. Both indirect comparisons matched on age, prostate-specific antigen level and doubling time, Eastern Cooperative Oncology Group performance status, Gleason score, and bone-sparing agent use. Darolutamide vs apalutamide also matched on prior surgery and darolutamide vs enzalutamide also matched on region. Risk differences and odds ratios were calculated for adverse events and hazard ratios for metastasis-free survival.
No differences in metastasis-free survival hazard ratios were found after matching in either comparison. However, fall, fracture, and rash rates were statistically significantly lower in favor of darolutamide vs apalutamide. Fall, dizziness, mental impairment, fatigue, and severe fatigue rates were statistically significantly lower in favor of darolutamide vs enzalutamide.
While metastasis-free survival did not differ across drugs in these cross-trial indirect comparisons, darolutamide showed a favorable safety and tolerability profile in pre-specified adverse events vs apalutamide and enzalutamide. Consideration of these adverse events is important in clinical decision-making and treatment selection in nonmetastatic castration-resistant prostate cancer.
The Journal of urology. 2021 Apr 05 [Epub ahead of print]
Susan Halabi, Shan Jiang, Emi Terasawa, Viviana Garcia-Horton, Rajeev Ayyagari, A Reginald Waldeck, Neal Shore
Duke University, Durham, North Carolina., Bayer, Whippany, New Jersey., Analysis Group, Inc., New York, New York., Analysis Group, Inc., Boston, Massachusetts., Carolina Urologic Research Center, Myrtle Beach, South Carolina.