Sex-based differences in tolerability of developmental antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC)

作者：Claudia Parisi, Marco Banini, Francesco Mantuano, M. Aldea, P. Abdayem, L. Derosa, M. Frelaut, P. Lavaud, A. Robert, S. Simon, A. Gazzah, A. Hollebecque, C. Massard, B. Besse, Jordi Remón, A. Wagner, Barbara Pistilli, I. Vaz-Luis, D. Planchard, F. Barlesi · 发表于：ESMO Open · 年份：2026 · DOI：10.1016/j.esmoop.2026.107773 · 被引用次数：1 · 研究领域：HER2/EGFR in Cancer Research、Lung Cancer Treatments and Mutations、Estrogen and related hormone effects

BACKGROUND: Sex-based differences in treatment-related adverse events (TRAEs) have been described across several anticancer therapies. However, sex-disaggregated safety data for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC) is lacking. PATIENTS AND METHODS: We conducted a monocentric cohort study including patients with advanced NSCLC treated with developmental ADCs within phase I-II clinical trials at Gustave Roussy (2018-2023). Clinically significant TRAEs (grade ≥2, Common Terminology Criteria for Adverse Events version 5.0), dose modifications, hospitalisations, and survival outcomes were analysed according to sex using univariate and multivariate analysis. RESULTS: Our population included 132 patients [women, 64 (48.5%); men, 68 (51.5%)] receiving ADCs targeting TROP2 (32.6%), ITGB6 (31.8%), HER2 (13.6%), CEACAM5 (13.6%), HER3 (5.4%), c-MET (2.3%), and Nectin-4 (0.7%). Overall, 100 (76%) and 39 (29%) patients experienced grade ≥2 and grade ≥3 TRAEs, respectively. Women had a higher incidence of grade ≥2 TRAEs than men [82.8% versus 69.1%; adjusted odds ratio (OR) 2.8, 95% confidence interval (CI) 1.03-7.84, P = 0.04)] and a higher median number of TRAEs (2 versus 1, P = 0.04). Metabolic TRAEs (anorexia, weight loss, ion and lipid imbalances) were significantly more frequent in women (29.7% versus 10.3%; OR 3.68, 95% CI 1.42-9.49, P = 0.009), as were dose reductions (37.5% versus 19.1%; OR 3.35, 95% CI 1.24-9.01, P = 0.02). CONCLUSIONS: Women treat...