Dermatologic adverse events associated with Sacituzumab Govitecan: an international retrospective study from the EADV Task Force "Dermatology for Cancer Patients" and pharmacovigilance analysis.

چکیده اصلی

PURPOSE: Sacituzumab govitecan (SG) is an antibody-drug conjugate approved across multiple metastatic breast cancer settings. Although hematologic and gastrointestinal toxicities dominate its safety profile, dermatologic adverse events (dAEs) remain poorly characterized, despite the physiological expression of Trop-2 in epidermal keratinocytes. We aimed to comprehensively characterize the spectrum, severity, time to onset, and oncologic impact of SG-associated dAEs across real-world and pharmacovigilance data sources. METHODS: An international retrospective cohort study was conducted within the EADV Task Force "Dermatology for Cancer Patients" (n = 56 breast cancer patients). Findings were triangulated with disproportionality analyses of the WHO Global Pharmacovigilance database (VigiBase®; n = 696 cases) and the French Pharmacovigilance Database (FPVD; n = 46 cases), alongside a literature review of SG clinical trials reporting dAEs. RESULTS: Across all data sources, alopecia was the most frequently reported dAE (EADV cohort: 41.1%; FPVD: 52.2%; VigiBase®: 67.6%), followed by stomatitis/mucositis, pruritus, xerosis, and maculopapular rash. In the EADV cohort, 13 distinct dAE types were identified; median time to first dAE was 56 days, and 96.4% of events were grade 1-2. Treatment discontinuation attributable to dAEs occurred in only 3.6% of patients. VigiBase® disproportionality analysis identified significant reporting signals for alopecia (IC 3.3 [3.09; 3.53]), infusion-related reactions (IC 1.9 [1.07; 2.55]), and stomatitis (IC 1.6 [0.86; 2.30]). Preliminary signals of cutaneous infections were observed but did not consistently meet the threshold for statistical significance. CONCLUSION: SG-associated dAEs are predominantly low-grade and infrequently precipitate treatment discontinuation. Pharmacovigilance data raises a potential signal for cutaneous infections that warrants further investigation. As SG increasingly enters combination regimens, structured dermatologic monitoring and prospective characterization of dAEs are essential to guide oncodermatologic management and protect oncological outcomes. CLINICAL TRIAL NUMBER: Not applicable.

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