Apalutamide-induced rash and relative dose intensity in metastatic castration-sensitive prostate cancer: a multicenter Japanese cohort study.

Background: Androgen receptor signaling inhibitors (ARSIs) have become the standard of care for metastatic castration-sensitive prostate cancer (mCSPC). However, Japanese patients treated with apalutamide experience dermatologic adverse events at higher rates than Western populations. This study aimed to identify clinical determinants of apalutamide-induced rash and evaluate the impact of treatment modification on relative dose intensity (RDI) and oncological outcomes. Methods: We retrospectively analyzed 95 patients with mCSPC treated with apalutamide plus androgen deprivation therapy (ADT) between February 2018 and April 2023. Patients who initiated therapy at reduced doses were excluded. The primary endpoint was the incidence of apalutamide-induced rash and its predictors. The secondary endpoint was the effect of RDI on progression-free survival (PFS), defined as time to castration-resistant prostate cancer (CRPC). Receiver operating characteristic analyses were used to identify risk factors for rash, and Cox proportional hazards models were used to assess predictors of progression. Results: Rash occurred in 38 patients (40%), including 13 (13.7%) with grade 3 events, with a median onset of 2 months. Older age [odds ratio (OR) =1.07, P=0.048] and lower body mass index (BMI; OR =0.89, P=0.049) were independent predictors. Cutoff values of age ≥ 68 years and BMI ≤19.7 kg/m Conclusions: Advanced age and low BMI are significant risk factors for apalutamide-induced rash in patients with mCSPC. Importantly, decreased RDI resulting from dose reduction or interruption did not compromise PFS, implying that timely dose modification may be a safe and effective strategy to manage adverse events without impairing oncological efficacy.