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

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.