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

IF 3.3 3区医学 Q2 ONCOLOGY

Breast Cancer Research and Treatment Pub Date : 2026-09-28 DOI:10.1007/s10549-026-08090-5

Ioannis-Alexios Koumprentziotis, Alexander Cawley, Elliot Ewig, Alexandre O Gérard, Maëlys Labat, Grażyna Kamińska-Winciorek, Marcin Kubeczko, Luca Rapparini, Michela Starace, Katerina Grafanaki, Maria Kamaratou, Dimitrios Mavroudis, Alexander Katoulis, Vasiliki Nikolaou, Kara Heelan, Dimitra Koumaki

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引用次数: 0

Abstract

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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与Sacituzumab Govitecan相关的皮肤不良事件：来自EADV工作组“癌症患者皮肤病学”和药物警戒分析的国际回顾性研究。

目的：Sacituzumab govitecan （SG）是一种被批准用于治疗多发性转移性乳腺癌的抗体-药物偶联物。虽然血液学和胃肠道毒性在其安全性方面占主导地位，但皮肤不良事件（dAEs）的特征仍然很差，尽管表皮角化细胞中有Trop-2的生理表达。我们的目的是在真实世界和药物警戒数据源中全面表征sg相关dAEs的频谱、严重程度、发病时间和肿瘤学影响。方法：一项国际回顾性队列研究由EADV“癌症患者皮肤病学”工作组进行（n = 56例乳腺癌患者）。研究结果与世卫组织全球药物警戒数据库（VigiBase®，n = 696例）和法国药物警戒数据库（FPVD, n = 46例）的歧化分析进行了三角分析，同时对报告dAEs的SG临床试验进行了文献综述。结果：在所有数据来源中，脱发是最常见的dAE报告（EADV队列：41.1%;FPVD: 52.2%; VigiBase®：67.6%），其次是口腔炎/粘膜炎、瘙痒、干燥症和斑疹。在EADV队列中，确定了13种不同的dAE类型；到首次dAE的中位时间为56天，96.4%的事件为1-2级。仅3.6%的患者因dAEs而停止治疗。VigiBase®歧化分析确定了脱发（IC 3.3[3.09; 3.53]）、输液相关反应（IC 1.9[1.07; 2.55]）和口炎（IC 1.6[0.86; 2.30]）的显著报告信号。观察到皮肤感染的初步信号，但没有一致地达到统计显著性的阈值。结论：sg相关的dAEs主要是低级别的，罕见的沉淀性停药。药物警戒数据提出了皮肤感染的潜在信号，值得进一步调查。随着SG越来越多地进入联合治疗方案，结构化的皮肤病学监测和dAEs的前瞻性表征对于指导皮肤肿瘤管理和保护肿瘤预后至关重要。临床试验号：不适用。

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来源期刊

Breast Cancer Research and Treatment 医学-肿瘤学

CiteScore

6.80

自引率

2.60%

发文量

342

审稿时长

1 months

期刊介绍： Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.