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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author 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
author_facet 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
author_sort Giulia Puliani
collection DOAJ
description 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.
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series European Thyroid Journal
spelling doaj-art-908babc8c76b426ea0934f1d6322a91c2025-08-20T03:53:32ZengBioscientificaEuropean Thyroid Journal2235-08022025-04-0114210.1530/ETJ-24-03861Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)Giulia Puliani0Marta Bianchini1Carlotta Giani2Laura Valerio3Alice Nervo4Giulia Sapuppo5Giorgio Grani6Cristina Dalmiglio7Simone De Leo8Rosa Lauretta9Marilda Mormando10Irene Terrenato11Stefania Zovato12Laura Fugazzola13Maria Grazia Castagna14Cosimo Durante15Gabriella Pellegriti16Emanuela Arvat17Rossella Elisei18Marialuisa Appetecchia19Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, ItalyOncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, ItalyDepartment of Clinical and Experimental Medicine, Endocrine Unit, Pisa University Hospital, Pisa, ItalyDepartment of Clinical and Experimental Medicine, Endocrine Unit, Pisa University Hospital, Pisa, ItalyOncological Endocrinology; Department of Medical Sciences; University of Turin, Turin, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalyDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Siena, ItalyEndocrine Oncology Unit, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, ItalyOncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, ItalyOncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, ItalyUOSD Clinical Trial Center, Biostatistic and Bionformatic, IRCCS Regina Elena National Cancer Institute, Rome, ItalyFamilial Cancer Clinic, Veneto Institute of Cancer, Istituto Oncologico Veneto IOV IRCCS, Padua, ItalyEndocrine Oncology Unit, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, ItalyDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Siena, ItalyDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, Catania, ItalyOncological Endocrinology; Department of Medical Sciences; University of Turin, Turin, ItalyDepartment of Clinical and Experimental Medicine, Endocrine Unit, Pisa University Hospital, Pisa, ItalyOncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, ItalyIntroduction: 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.https://etj.bioscientifica.com/view/journals/etj/14/2/ETJ-24-0386.xmllenvatinibsexgenderefficacysafetyradioiodine-refractory differentiated thyroid cancer
spellingShingle 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
Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)
European Thyroid Journal
lenvatinib
sex
gender
efficacy
safety
radioiodine-refractory differentiated thyroid cancer
title Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)
title_full Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)
title_fullStr Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)
title_full_unstemmed Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)
title_short Gender impact on safety and efficacy in lenvatinib treated patients with radioiodine-refractory differentiated thyroid cancer (GISEL study)
title_sort gender impact on safety and efficacy in lenvatinib treated patients with radioiodine refractory differentiated thyroid cancer gisel study
topic lenvatinib
sex
gender
efficacy
safety
radioiodine-refractory differentiated thyroid cancer
url https://etj.bioscientifica.com/view/journals/etj/14/2/ETJ-24-0386.xml
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