Post Hoc Subgroup Analysis of Clinical Outcomes in Patients With High‐Risk Metastatic Hormone‐Naïve Prostate Cancer: Results From a 3‐Year Interim Analysis of the J‐ROCK Study

ABSTRACT Introduction In real‐world practice in Japan, standard treatment for metastatic hormone‐naïve prostate cancer (mHNPC) is androgen deprivation therapy (ADT), administered as monotherapy, combined androgen blockade (CAB), ADT plus androgen receptor pathway inhibitors (ARPIs), or ADT plus docetaxel. In a previous interim analysis of the large‐scale, longitudinal, multicentre, J‐ROCK registry study of real‐world clinical and patient‐reported outcomes, ADT plus ARPI or ADT plus docetaxel was used more frequently than ADT/CAB in patients (aged ≥ 20 years) with newly diagnosed LATITUDE‐criteria high‐risk mHNPC. Methods This post hoc analysis of the J‐ROCK study evaluated prostate‐specific antigen (PSA) response, progression‐free survival (PFS), time to castration‐resistant prostate cancer (CRPC), overall survival (OS) and safety in patients with high‐risk mHNPC who received ADT/CAB (cohort 1) or ADT plus ARPI (cohort 2B) in subgroups were defined according to the following known prognostic factors at baseline: age, Gleason Grade Group (GGG), alkaline phosphatase (ALP), hemoglobin (Hb) and lactate dehydrogenase (LDH). Results This analysis included 947 evaluable patients (371 in cohort 1 and 576 in cohort 2B). PSA response rates remained similar among age and GGG subgroups in both cohorts, but were reduced in cohort 2B patients with elevated ALP, low Hb, and elevated LDH. Time to CRPC and OS were longer in cohort 2B than in cohort 1, regardless of prognostic factors. Among patients with poor prognosis (older, high GGG, low Hb, elevated LDH), OS decline occurred earlier in cohort 1 versus cohort 2B. A trend towards a plateau in the time to CRPC curve was observed in both cohorts, even in patients with poor prognosis. Safety data were not affected by prognostic factors or treatment. Conclusions These findings suggest that novel ADT plus ARPI regimens for LATITUDE‐criteria high‐risk mHNPC may improve real‐world outcomes compared with ADT monotherapy or CAB, particularly among patients with poor prognosis.