OBJECTIVES: Apalutamide (APA) and darolutamide (DARO), both combined with androgen deprivation therapy (ADT), have been compared with ADT in the respective SPARTAN and ARAMIS randomised trials. In the absence of head-to-head trials, both agents are compared indirectly.

METHODS: Patient-level data from SPARTAN (first interim analysis [IA1]) and published data from ARAMIS (IA1) were utilized. SPARTAN patients were weighted to match baseline characteristics as reported for ARAMIS in an anchored MAIC, using ADT as the common treatment arm. First, hazard ratios (HRs) for efficacy end-points metastasis-free survival (MFS), progression-free survival (PFS), prostate-specific antigen (PSA) progression and overall survival (OS), and odds ratios for tolerability were re-estimated for SPARTAN using weighted Cox proportional hazards and logistic regression models. Next, the reweighted SPARTAN results were indirectly compared with reported HRs and ORs from ARAMIS using a Bayesian framework.

RESULTS: A total of 1,150 SPARTAN patients were included and assigned weights to match the ARAMIS population (N=1,509). MAIC-based HRs (95% confidence interval) for SPARTAN were significant in favor of APA+ADT vs ADT at 0.29 (0.22, 0.38) for MFS, 0.30 (0.23, 0.39) for PFS, 0.06 (0.05, 0.08) for PSA progression, and indicated a favorable trend for OS (HR = 0.75 [0.45, 1.23]). MAIC-based HRs (95% confidence interval) for APA+ADT vs DARO+ADT were 0.70 (0.51, 0.98) for MFS, 0.79 (0.59, 1.08) for PFS, 0.46 (0.33, 0.64) for PSA progression, and 1.05 (0.58, 1.93) for OS. The Bayesian probabilities of APA+ADT being more effective than DARO+ADT were 98.3% for MFS, 93.1% for PFS, ~100% for PSA progression, and 43.5% for OS. The MAIC results indicated comparable tolerability profiles for APA and DARO.

CONCLUSIONS: Based on available data and Bayesian probabilities, results suggest that nmCRPC patients treated with APA+ADT had more favorable MFS, PFS, and PSA progression than those who received DARO+ADT with comparable tolerability of the treatments.