Apalutamide-induced severe cutaneous adverse reactions in prostate cancer: a comprehensive review of reported cases and clinical strategies

Purpose: Prostate cancer (PCa) is the most common fatal malignancy among men and a major cause of cancer-related death. Apalutamide, a second-generation androgen receptor inhibitor, is approved for non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). However, an increasing number of potentially life-threatening severe cutaneous adverse reactions (SCARs) associated with apalutamide have raised clinical concerns. This review aims to characterize apalutamide-induced SCARs and summarize effective management strategies based on reported cases. Materials and methods: We systematically searched PubMed, Europe PMC, and CNKI for case reports of SCARs associated with apalutamide. Keywords included "Apalutamide" and "Drug eruptions." A total of 18 cases were identified and analyzed. Results: We reviewed the clinical characteristics and treatment of 3 cases of DRESS, 14 cases of SJS/TEN, and 1 case of AGEP, all highly suspected to be caused by apalutamide, reported globally. The most frequent SCARs associated with apalutamide are SJS/TEN. The median onset time of SCARs in these cases was 39.5 days, significantly shorter than the onset time of rash in phase III clinical trials of apalutamide. Geographically, the majority of reported cases originated from East Asia. By analyzing the treatment regimens and clinical outcomes of these patients, combined with a literature review, we proposed a set of definitive therapeutic strategies. Conclusion: Apalutamide-induced SCARs tend to occur earlier than common rashes observed in clinical trials, with a predominance of reported cases in East Asian populations. Immediate discontinuation of the suspected drug is the cornerstone of SCAR management. Supportive care, systemic corticosteroids, intravenous immunoglobulin (IVIG), cyclosporine, plasmapheresis, and TNF-α antagonists play important roles in treatment. Personalized dosing strategies based on body weight or body surface area, along with proactive rash management, may help mitigate risk and optimize therapeutic continuity.