Age-stratified clinical outcomes and adverse events in patients with metastatic castration-sensitive prostate cancer receiving triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel

Background: Triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel (DOC) has emerged as an intensified treatment option for metastatic castration-sensitive prostate cancer (mCSPC). This study evaluated real-world prostate specific antigen (PSA) responses and adverse events (AEs) associated with triplet therapy, with a focus on age-specific differences. Methods: We performed a retrospective cohort study across six academic institutions in Japan between February 2023 and February 2025. A total of 137 patients with mCSPC who received triplet therapy were analyzed. PSA responses and AEs were assessed, including subgroup analyses by age (<75 vs ≥75 years). Results: The median age was 71 years, and 40 patients (29.2%) were aged ≥75 years. Six cycles of DOC were completed at similar rates in patients aged <75 years (66.0%) and ≥ 75 years (57.5%) (P = .435). The median baseline PSA was 298 ng/ml, and 107 patients (78.1%) met the CHAARTED high-volume criteria. At three months, the median [interquartile range] PSA decline was 99.8% [99.0–99.9]; 113 patients (92.6%) achieved a PSA decline >90%, and 35 patients (28.7%) achieved a PSA <0.2 ng/ml. During follow-up, the proportion achieving a PSA nadir <0.2 ng/ml did not differ significantly between patients aged <75 years (63.9%) and ≥ 75 years (55.0%) (P = .341). Grade ≥ 3 AEs occurred in 56 patients (40.9%), including febrile neutropenia in 29 patients (21.2%). The incidence of AEs did not differ significantly by age. Conclusions: In this real-world cohort, triplet therapy showed substantial PSA declines and acceptable tolerability, with no significant differences in short-term efficacy or safety between patients aged <75 and ≥ 75 years. These findings suggest that chronological age alone should not preclude consideration of triplet therapy in appropriately selected patients.