Effect of apalutamide dosage on the incidence of cutaneous adverse events and prostate-specific antigen reduction in patients with prostate cancer.

Apalutamide (Erleada®; Janssen-Cilag Ltd.; Johnson & Johnson) is an effective therapeutic agent for prostate cancer; however, adverse events, particularly cutaneous toxicity, may lead to treatment discontinuation. Among Japanese patients, the incidence of cutaneous toxicity is relatively high and increased drug exposure has been reported in individuals with a small body size. In the present retrospective study, the effects of a reduced dose of apalutamide with stepwise escalation on the incidence of cutaneous toxicity and treatment efficacy were evaluated. Patients with prostate cancer who received apalutamide at Ogaki Municipal Hospital (Ogaki, Japan) between May 2019 and September 2024 were included in the present study. Based on their initial dose, patients were categorized into the standard-dose (240 mg; n=26) or reduced-dose (120 or 180 mg; n=20) group. The incidence and severity of cutaneous toxicity, time to the first cutaneous event and time to achieve prostate-specific antigen (PSA) <0.2 ng/ml and progression-free survival (PFS) were compared. Cutaneous toxicity occurred in 73.1 and 40.0% of the standard-dose and reduced-dose groups, respectively (P=0.036). Grade ≥3 toxicity was observed only in the standard-dose group (11.5%). The median time to the first cutaneous event was 63.0 vs. 45.5 days (P=0.193). The median time to achieve PSA <0.2 ng/ml was 120.0 days in both groups (P=0.822). The median PFS was not reached in the standard-dose group but was 693 days in the reduced-dose group (P=0.116). Overall, initiating apalutamide at a reduced dose with gradual escalation may mitigate the risk of cutaneous toxicity without compromising the PSA response. These findings provide clinically relevant insights, particularly for patients with a small body size, however further demonstration in larger prospective studies is warranted.