SUMMARY  

• Rare postmarketing cases of severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), which can be life-threatening or may lead to death, have been reported with ERLEADA. Discontinue ERLEADA immediately if signs or symptoms of a SCAR develop.¹ Please refer to local labeling for additional considerations and data.
  • DRESS frequency was 11 cases/48,249 person-years or 2.3 cases/10,000 personyears (through 25 Feb 2022). These cases were reported in France, Japan, Singapore, Belgium, China, and Switzerland.²
    • Of the 11 cases, 2 cases were considered as potentially representative of DRESS with causality assessed as possibly related to ERLEADA.
  • SJS/TEN frequency was 30 cases/38,906 person-years or 7.71 cases/10,000 personyears (through 15 Oct 2021). These cases were reported globally (including 4 in the US) with 19 cases from Japan.³
• There were no events of DRESS, SJS, or TEN reported with ERLEADA in the phase 3, randomized, placebo-controlled, registrational TITAN (N=1052) and SPARTAN (N=1207) studies in patients with metastatic castration-sensitive prostate cancer (mCSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC), respectively.^4-6
• In the phase 2 APA-RP study in treatment-naïve patients with high-risk localized prostate cancer who had undergone radical prostatectomy (N=108), SJS was reported as a treatment-emergent serious adverse event (AE) in 1 patient (0.9%) receiving ERLEADA plus androgen deprivation therapy (ADT).⁷
• Published case reports and retrospective studies related to SCARs in patients receiving ERLEADA were identified in the literature.^8-23
• SCARs have been reported with ERLEADA use based on real-world postmarketing data from select regulatory agency databases.^15,24
• A review article was additionally identified to assess characteristics of mild and severe ERLEADA-related cutaneous AEs per onset time and lymphocyte transformation test results in patients with prostate cancer.²⁵

POSTMARKETING SAFETY

Case Reports and Retrospective Studies

Published case reports, including fatal cases, were identified in the literature for ERLEADA and SCARs.^8-20 SCAR types included DRESS, acute generalized exanthematous pustulosis (AGEP), SJS, and/or TEN. Dosage regimen, onset, concomitant medications, clinical characteristics, intervention/management, and/or outcomes are reported in the respective publications.

Three separate retrospective studies in Japan reported ERLEADA-associated SCARs in patients with prostate cancer: one grade 5 TEN event, one case of AGEP, and one fatal case of TEN-related multiple organ failure.^21-23

Postmarketing Safety Databases

SCARs have been reported with ERLEADA use based on published real-world postmarketing data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Disproportionality analyses were used to identify AE signals in reports where ERLEADA was documented as primary or secondary suspect from the first quarter of 2018 to the first quarter of 2022. Preferred Terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA) and reporting odds ratio (ROR) were used for identifying signals indicating a potentially increased risk of drug-associated AEs. Of 4156 total AE reports, 24 AEs of TEN (ROR of 14.46 [95% confidence interval (CI), 9.68-21.60]), 17 AEs of DRESS (ROR of 4.55 [95% CI, 2.82-7.32]), 11 AEs of SJS (ROR of 5.66 [95% CI, 3.13-10.24]), and 5 AEs of AGEP (ROR of 5.06 [95% CI, 2.10-12.16]) were reported.¹⁵

In a published analysis of SJS and TEN data in the Russian National Pharmacovigilance database of spontaneous events from April 2019-December 2023, 1 (2.1%) elderly patient receiving ERLEADA had SJS/TEN.²⁴

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 12 November 2024.