CE1 A Modeled Health Outcomes Evaluation of Darolutamide Plus Androgen Deprivation Therapy for High-Risk NON-Metastatic Castration-Resistant Prostate Cancer in China

Abstract

Novel antiandrogens have demonstrated clinical benefit for patients with non-metastatic castration resistant prostate cancer (nmCRPC). We modeled the incremental life-years and QALYs of darolutamide+ADT compared to apalutamide+ADT and enzalutamide+ADT, for high-risk nmCRPC, in a Chinese setting. A partitioned survival model with three health states (nmCRPC, metastatic CRPC and death) was devised. Data from the ARAMIS, PROSPER and SPARTAN trials were used, in the absence of head-to-head studies. Hazard ratios (HRs) characterizing overall survival (OS) were derived from formal indirect treatment comparisons of the OS HRs between the three trials; the point estimates of the OS HRs characterizing the indirect comparison of darolutamide+ADT vs apalutamide+ADT and enzalutamide+ADT were 0.88 and 0.95, respectively. Parametric survival functions were selected for extrapolation based on the goodness of fit. The baseline characteristics, treatment patterns and utilities for this modeled Chinese cohort were validated with 12 urologists from 11 hospitals. A discount rate of 5% was applied. Univariate and probabilistic sensitivity analyses were performed. With a 20-year modeling horizon, darolutamide+ADT yielded more life years (5.98LYs) and QALYs (4.61QALYs) than both apalutamide+ADT (5.64LYs, 4.43QALYs) and enzalutamide+ADT (5.82LYs, 4.55QALYs). The incremental QALY gains with darolutamide+ADT vs. apalutamide+ADT (+0.18QALYs) and vs. enzalutamide+ADT (+0.06QALYs) were mainly driven by the improved life years during post-progression survival (+0.92LYs vs. apalutamide+ADT and +0.65LYs vs. enzalutamide+ADT). Results were sensitive to the HRs and utility inputs; however, the probabilities of darolutamide+ADT having incremental QALYs reached 70.4% and 56.8% when compared to apalutamide+ADT and enzalutamide+ADT, respectively. This modeled evaluation indicates that darolutamide+ADT is likely to be associated with incremental health outcomes over apalutamide+ADT and enzalutamide+ADT, for a high-risk nmCRPC Chinese cohort, over a 20-year time-frame.