Enzalutamide induced acute generalized exanthematous pustulosis

Alberto, Chloé; Konstantinou, Maria Polina; Martinage, C; Casassa, E.; Tournier, É.; Bagheri, Haleh; Sibaud, V.; Mourey, Loïc; Mazereeuw‐Hautier, J.; Meyer, Nicolas; Paul, C.; Livideanu, Cristina Bulai

doi:10.3315/jdcr.2016.1226

Cited by 16 publications

(4 citation statements)

References 7 publications

(5 reference statements)

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“…Recently, the National Comprehensive Cancer Network (NCCN) guidelines were updated to recommend apalutamide or enzalutamide, another second-generation antiandrogen, in patients with nmCRPC with background ADT therapy [ 11 ]. Skin rash was not observed to be an adverse drug reaction (ADR) in Phase 3 trials, either in nmCRPC or mCRPC patients [ 12 , 13 ] with enzalutamide, although a case report of enzalutamide-induced acute generalized exanthematous pustulosis was recently reported and the USPI includes rash as an ADR observed in post-marketing [ 14 ]. Skin rash has also been reported with the first-generation oral non-steroidal antiandrogen drug bicalutamide and other new-generation oral antiandrogen drugs such as darolutamide [ 15 – 18 ].…”

Section: Discussionmentioning

confidence: 99%

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

Uemura

Koroki²,

Iwaki³

et al. 2020

BMC Urol

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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.

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Section: Discussionmentioning

confidence: 99%

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

Uemura

Koroki²,

Iwaki³

et al. 2020

BMC Urol

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“…We could only find two other cases of cutaneous adverse events to androgen receptor inhibitors in the English literature ( Table 1 ) ( 16 , 17 ). These two cases reported that skin lesions were noticed within two weeks after starting enzalutamide and were improved after hormone therapy.…”

Section: Discussionmentioning

confidence: 98%

Stevens-Johnson Syndrome Caused by Enzalutamide: A Case Report and Literature Review

et al. 2021

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ObjectiveEnzalutamide is the most frequently prescribed compound for treating metastatic castration-resistant prostate cancer (mCRPC). Common adverse drug events of enzalutamide are febrile neutropenia, hot flashes, hypertension, and fatigue.MethodsWe present a case of a patient with mCRPC who received enzalutamide and developed Stevens-Johnson syndrome (SJS). The culprit drug was confirmed using the Naranjo Adverse Drug Reaction Probability Scale. Clinical characteristics and management principles were analyzed in combination with literature reports.ResultsSJS occurred within two weeks of enzalutamide therapy. Supportive care such as steroid treatment led to a complete resolution of skin lesions and improved clinical symptoms after three weeks.ConclusionMost cutaneous adverse events occur early during enzalutamide therapy, and close observation should be given within two weeks of starting treatment.

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“…[11] Skin rash was not observed to be an adverse drug reaction (ADR) in Phase 3 trials, either in nmCRPC or mCRPC patients [12,13] with enzalutamide, although a case report of enzalutamide-induced acute generalized exanthematous pustulosis was recently reported and the USPI includes rash as an ADR observed in post-marketing. [14] Skin rash has also been reported with the rst-generation oral non-steroidal antiandrogen drug bicalutamide and other new-generation oral antiandrogen drugs such as darolutamide. [15][16][17][18] It remains to be elucidated if skin rash is a class-effect, particularly in Japanese patients.…”

Section: Discussionmentioning

confidence: 99%

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

Uemura

Koroki

Iwaki

et al. 2020

Preprint

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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 hours) (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

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Enzalutamide induced acute generalized exanthematous pustulosis

Cited by 16 publications

References 7 publications

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

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

Stevens-Johnson Syndrome Caused by Enzalutamide: A Case Report and Literature Review

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

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