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 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. Results 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. 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, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment. Trial registration Retrospective pooled analysis of NCT01946204, NCT02489318, and NCT02162836.

Dermatological Adverse Events in Prostate Cancer Patients Treated with the Androgen Receptor Inhibitor Apalutamide

“…7,8 Our findings are not comparable to the analysis of the Japanese cohort from the SPARTAN and TITAN trials for all grade (51.5%) and grade 3 (14.7%) rashes. 14 Time to onset of dAEs post exposure was similar to the SPARTAN trial (median of 82 days) and an integrated analysis (median of 66 days). 8,14…”

“…14 Time to onset of dAEs post exposure was similar to the SPARTAN trial (median of 82 days) and an integrated analysis (median of 66 days). 8,14…”

“…In the SPARTAN trial and a subset of Japanese patients, maculopapular rash was also the most prevalent morphology. 8,14 While high reports of xerosis may be due to a post-inflammatory state following a drug reaction, concomitant ADT and the cohort’s older age may also be contributing factors. Lipid and sebum production necessary for proper skin barrier function is largely influenced by androgens.…”

“…In pharmacokinetic studies of apalutamide, those with rash had higher plasma concentrations of an active metabolite N-desmethyl apalutamide than those without rash. 14 While no pharmacokinetic analyses of N-oxide abiraterone sulphate exist in those with rash, future research could assess this compound’s significance in abiraterone-related dAEs.…”

Correction to: 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

“…In the original publication of this article [1] there were several errors in Table 1 related to the values for Disease status (nmCRPC and mCSPC). In this correction article the correct and incorrect values are shown.…”