Preliminary Report on the Efficacy and Safety of Triplet Therapy in Patients With Metastatic Hormone‐Sensitive Prostate Cancer: YUSHIMA Study

ABSTRACT Background The phase 3 ARASENS and PEACE‐1 studies demonstrated significant survival benefits from triplet therapy (androgen deprivation therapy [ADT] plus androgen receptor signaling inhibitor plus docetaxel) versus ADT plus docetaxel alone. We examined the efficacy and safety of triplet therapy using the prospective observational clinical study: YUSHIMA study database. Methods We analyzed data on patients with metastatic hormone‐sensitive prostate cancer (mHSPC) treated with triplet therapy extracted from the YUSHIMA study database. Deep and early prostate‐specific antigen (PSA) response was defined as ≥ 90% PSA decline or PSA ≤ 0.2 ng/mL achievable at 3 months of treatment. Kaplan–Meier curves were used to assess overall survival (OS) and castration‐resistant prostate cancer (CRPC)–free survival. Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events version 5.0. Results Overall, 317 patients were enrolled in the YUSHIMA study from 2021 to 2025, of which 48 received triplet therapy. Organ metastases accounted for 25%. According to the CHAARTED and LATITUDE criteria, 77% and 73% of patients exhibited high‐volume and high‐risk disease, respectively. The 1‐year OS and CRPC‐free survival rates were 88% and 79%, respectively. Deep and early PSA response was achieved in 98%. In our cohort, grade 3–4 AEs appeared in 89% of cases, most of which were neutropenia. In 20% of cases, 6 courses of docetaxel could not be completed due to AEs. Conclusions Triplet therapy was highly efficacious and tolerable in Japanese mHSPC patients. Although most patients experienced grade 3–4 neutropenia, no cases were fatal. The deep and early PSA response represents a satisfactory short‐term result.