A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC).
This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN ( NCT01946204 ; patients with non-metastatic 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.
Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. 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. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 h) (AUC0-24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without.
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, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment.
Retrospective pooled analysis of NCT01946204 , NCT02489318 , and NCT02162836 .
BMC urology. 2020 Sep 02*** epublish ***
Hiroji Uemura, Yosuke Koroki, Yuki Iwaki, Keiichiro Imanaka, Takeshi Kambara, Angela Lopez-Gitlitz, Andressa Smith, Hirotsugu Uemura
Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan., Medical Affairs, Janssen Pharmaceutical K.K., Tokyo, Japan. ., Clinical Pharmacology, Janssen Pharmaceutical K.K, Tokyo, Japan., Clinical Science, Janssen Pharmaceutical K.K, Tokyo, Japan., Department of Dermatology, Yokohama City University Medical Center, Yokohama, Japan., Janssen Global Research & Development, Spring House, PA, USA., Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan.