133 Background: Triplet combination of darolutamide (DARO; an androgen receptor inhibitor) with androgen deprivation therapy (ADT), and docetaxel significantly improved overall survival (OS; HR 0.68; 95% CI 0.57–0.80; P <0.001) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS trial (NCT02799602). DARO also showed benefit of intensified therapy in maximizing efficacy while minimizing toxicity. Q-TWiST is an approach that compares variation in efficacy and toxicity between treatment arms. This study assessed quality of life-adjusted survival of patients with mHSPC using DARO triplet therapy compared with doublet therapy (ADT and docetaxel). Methods: The Q-TWiST method assumes patients progress through a set of three health states. Time Without Symptoms or Toxicity (TWiST), time in RELapse or disease progression (REL), and time with TOXicity (TOX; with grade 3/4 symptoms or toxic effects) were estimated by the 53-month restricted mean using grade 3/4 adverse event (AE), OS, and time to castration-resistant prostate cancer (CRPC) data from ARASENS. Q-TWiST was calculated as the weighted sum of time spent in each health state for each treatment arm (DARO vs placebo PBO), adjusted by corresponding utility scores obtained from published sources. Differences in mean Q-TWiST between treatment arms were calculated for utility weights. For each health state, 95% CIs and mean standard errors (SEs) of TWiST, REL, TOX, and Q-TWiST were calculated based on 1000 bootstrap samples. Relative gain in Q-TWiST was calculated by dividing the mean Q-TWiST difference between treatment arms by the restricted mean OS of the PBO arm. Results: The full analysis set included 651 and 654 patients in the DARO and PBO arms, respectively. Patients had similar incidence of grade 3/4 AEs prior to disease progression (47.5% vs 53.2%), lower incidence of CRPC (34.6% vs 59.8%), and improved OS (deaths: 35.2% vs 46.5%) with DARO vs PBO. Significantly, patients had 6.3 months more Q-TWiST with DARO vs PBO driven by an increase in TWiST (mean 17.6 months SE 0.9 vs 10.9 months 0.7), and less REL (2.4 months 0.3 vs 8.7 months 0.4); due to the long treatment duration, there was more TOX (17.2 months 0.9 vs 11.3 months 0.7) at 53 months (all P <0.001). Partitioned Kaplan–Meier survival curves showed significantly persistent TWiST with DARO vs PBO indicating patients spent more time without grade 3/4 AEs before disease progression ( P <0.001). The DARO Q-TWiST relative gain was 16.0% (clinically important). Conclusions: In ARASENS, DARO triplet therapy provided an additional 6.3 months of OS without symptoms or toxicity and a Q-TWiST relative gain of 16.0% corresponding to higher overall quality-adjusted survival vs doublet therapy at 53 months. This highlights the benefit of the standard of care ARASENS regimen for patients with mHSPC. Clinical trial information: NCT02799602 .
Maiorano et al. (2026) studied this question.