Long-term Longitudinal Observation of Lenvatinib-associated Adverse Events in Patients With Unresectable Radioiodine-refractory Differentiated Thyroid Cancer

Yuka Aida; Toshio Suzuki; Yusuke Watanabe; Sachie Hashimoto; Emika Ichioka; Akiko Iguchi-Manaka; Joichi Usui; Masato Homma; Hisato Hara; Ikuo Sekine

doi:10.1111/ajco.14211

Long-term Longitudinal Observation of Lenvatinib-associated Adverse Events in Patients With Unresectable Radioiodine-refractory Differentiated Thyroid Cancer

Asia Pac J Clin Oncol. 2025 Jun 30:e14211. doi: 10.1111/ajco.14211. Online ahead of print.

Authors

Affiliations

¹ Department of Medical Oncology, University of Tsukuba Hospital, Tsukuba, Japan.
² Department of Pharmacy, University of Tsukuba Hospital, Tsukuba, Japan.
³ Department of Breast and Endocrine Surgery, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
⁴ Department of Nephrology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.

PMID: 40586274
DOI: 10.1111/ajco.14211

Abstract

Aim: To characterize the long-term adverse events (AEs) observed in patients who received lenvatinib.

Methods: We longitudinally assessed long-term AEs in patients with advanced or metastatic radioiodine-refractory differentiated thyroid cancer who had received lenvatinib for more than 1 year. AEs were graded according to the National Cancer Institute Common Terminology Criteria for AEs. Grade 2 AEs were defined as intolerable if a patient complained of distress.

Results: Seventeen patients were treated for more than 1 year. The median age was 69 years. The median duration of lenvatinib treatment was 40 months. Notable intolerable grade 2 and 3 AEs were developed in the following order: hypertension (median day 18; range, day 1-131), diarrhea (median, day 27; range, day 4-1205), hand-foot skin reaction (median, day 33; range, day 20-582), platelet decrease (median, day 57; range, day 15-427), proteinuria (median, day 72; range, day 18-1772), anorexia (median, day 319; range, day 57-1541), and chronic kidney disease (CKD) (median, day 715; range, day 274-1296). After 2 years of administration, the decrease in estimated glomerular filtration rate became remarkable. Grade 3 hypertension occurred in 94.1% (16/17) of patients, of whom 66.8% (11/16) developed intolerable grade 2 proteinuria at a median interval of 35 days. Of these patients, 54.5% (6/11) developed intolerable grade 2 CKD at a median interval of 245 days.

Conclusions: This longitudinal study revealed which AEs appeared and when. The findings provide useful information about when and which AEs we should be attentive to during daily practice.

Keywords: anorexia; chronic kidney disease; hand‐foot skin reaction; hypertension; proteinuria.