Skin Rash Following Administration of Apalutamide in Japanese Patients with Advanced Prostate Cancer: An Integrated Analysis of the Phase 3 SPARTAN and TITAN Studies and a Phase 1 Open-Label Study
Abstract Background A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC).Methods This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with nonmetastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio.Results Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analysed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0–24 hours) (AUC0 − 24ss) at steadystate of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without.Conclusions No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamiderelated skin rash is easily managed, with appropriate treatment with or without dose adjustment.