Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)

Introduction: Little is known about sex differences in lenvatinib treatment safety and efficacy. Methods: Real-word retrospective Italian multicenter study enrolling patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib. Results: A total of 138 patients (64 femal...

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Main Authors: Giulia Puliani, Marta Bianchini, Carlotta Giani, Laura Valerio, Alice Nervo, Giulia Sapuppo, Giorgio Grani, Cristina Dalmiglio, Simone De Leo, Rosa Lauretta, Marilda Mormando, Irene Terrenato, Stefania Zovato, Laura Fugazzola, Maria Grazia Castagna, Cosimo Durante, Gabriella Pellegriti, Emanuela Arvat, Rossella Elisei, Marialuisa Appetecchia
Format: Article
Language:English
Published: Bioscientifica 2025-04-01
Series:European Thyroid Journal
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Online Access:https://etj.bioscientifica.com/view/journals/etj/14/2/ETJ-24-0386.xml
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Summary:Introduction: Little is known about sex differences in lenvatinib treatment safety and efficacy. Methods: Real-word retrospective Italian multicenter study enrolling patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib. Results: A total of 138 patients (64 females) were included, with a median follow-up of 26 months (2–72). More men performed physical activities (34% vs 17%, P = 0.024). The frequency of smoking and alcohol consumption was higher in men (58% vs 33%, P = 0.003; 45% vs 17%, P = 0.001). We did not find sex differences in lenvatinib dose reduction due to adverse events (AEs) (78% females vs 85% males). Ninety-nine percent of patients developed at least one adverse event (AE), with no sex difference in their number and the time to first AE. Severe AEs occurred in 74% of males and 66% of females (P = 0.398), with a mean dose of 18.2 mg (±5.7), and a median time to the first serious AE of 9 weeks (1–154). Stomatitis/mucositis and hematological disorders were more frequent in females (48% vs 30%, P = 0.016; 17% vs 4%, P = 0.011). Gastrointestinal disorders were higher in males (15% vs 2%, P = 0.010). Eighty-seven patients interrupted lenvatinib due to AEs (median time: 3 months (0–48), mean dose: 17 mg ±5.5). Discontinuation occurred in 21 patients, five for severe AEs. No sex differences were found in progression-free survival, overall survival or disease control rate. Liver metastases were associated with disease progression (HR: 3.73, 95% CI: 1.06–13.12, P = 0.040) or death (HR: 4.82, 95% CI: 1.75–13.25, P = 0.002) only in females. Conclusion: Lenvatinib is effective in both sexes and exhibits a good safety profile, with a sex difference in the frequencies of some adverse events.
ISSN:2235-0802