Association of Initial Adjustment Dose of Apalutamide with Progression to Castration-Resistant Prostate Cancer and Skin-Adverse Events in Men with Metastatic Castration-Sensitive Prostate Cancer: A Multicenter Retrospective Study of CsJUC Cohort.

137 Background: Japanese patients with prostate cancer (PC) treated with apalutamide often encounter skin-adverse events (AE), which might lead to adjust the initial-dose of apalutamide. However, concerns have emerged regarding the potential impact of these dose adjustments on the overall efficacy of apalutamide in real-world clinical practice. We aimed to evaluate the association between adjustment of apalutamide dose and clinical outcome in Japanese men with metastatic castration-sensitive PC (mCSPC). Methods: We retrospectively evaluated 108 mCSPC patients treated with apalutamide. We divided patients into two groups: initial full-dose and reduced-dose recipients. The primary outcome was the impact of apalutamide dose adjustment on progression to castration-resistant prostate cancer (CRPC) and PSA response. The secondary outcomes were the impact of apalutamide dose adjustment on the incidence of the skin-AE. Results: Initial reduced-dose recipients of apalutamide were observed in 16.7%. There were no differences in cancer characteristics, such as CHAARTED criteria between the groups. Initial full-dose recipients were significantly associated with a longer time to CRPC than initial reduced-dose recipients [median NA (NA - NA) vs. 19 months (95% CI, 10 - NA), P=0.0161], although the percentages of the initial full-dose recipients who reduced apalutamide dose were 30%, 44.4%, 60%, and 63.3% at 3, 6, 9, and 12 months, respectively. The percentage of PSA <0.2 decline at 3 months did not differ between the groups (59.1% vs 50%, P=0.602), but overall PSA 90% decline was higher in the initial full-dose recipients (88.8% vs 66.7%, P=0.027). Skin-AE occurred 50% in initial reduced-dose recipients and 51.1% in initial full-dose recipients, with no difference between the groups (P>0.999). Furthermore, time to skin-AE was not different between the groups (74 days vs. 69 days, P=0.992). Conclusions: Our study suggested the potential negative implications of initial apalutamide dose adjustments on clinical outcomes in Japanese men with mCSPC.