OBJECTIVES: This study compared adverse event (AE) profiles, costs, and metastasis-free life years (MFLY) gained for patients receiving nmCRPC treatment with SGARI therapies.

METHODS: We used a cohort-based Markov model with a three-year time horizon to simulate the treatment effects of darolutamide, enzalutamide, and apalutamide. Using a three-month time cycle, the model tracked the percent of patients still on treatment, discontinued due to AEs, and metastasized or died.

The model calculated results for three AE scenarios (AS). Baseline: grade 3-5 AEs reported in all 3 trials, minimum 1% incidence in one treatment arm. AS1: grade 3-5 AEs reported in at least 2 trials, minimum 1% incidence in one treatment arm. AS2: grade 3-5 AEs in all 3 trials, no incidence threshold.

AE costs were calculated using Healthcare Cost and Utilization Project 2018 data, inflated to 2021 USD, with a 3% discount rate. Incremental AE rates and MFLY were estimated from each treatment’s pivotal trial, compared to each respective placebo arm.

RESULTS: AEs included in the baseline scenario were diarrhea, fall, fatigue (excluding asthenia), hypertension, and weight loss. The highest incremental AE rate reported in each clinical trial was 0.9% (hypertension) for darolutamide, 3.0% (hypertension) for enzalutamide, and 4.9% (rash) for apalutamide.

Reflective of consistently lower rates of AEs, incremental per-patient AE costs over the 3-year time horizon were lowest for darolutamide in all three scenarios. Baseline: darolutamide, $53; enzalutamide $432; apalutamide, $517. AS1: darolutamide, $64; enzalutamide $670; apalutamide, $1,140. AS2: darolutamide, $69; enzalutamide $506; apalutamide, $553.

MFLY gained were similar across the treatments, with darolutamide having the greatest per-patient at 0.41 compared to apalutamide (0.39) and enzalutamide (0.38).

CONCLUSIONS: Darolutamide offered lower AE costs and similar efficacy relative to apalutamide and enzalutamide in nmCRPC. The lower costs may translate to significant savings for payers and improved patient quality of life.