Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study

BackgroundRadioactive iodine (RAI) is the standard treatment for distant metastatic differentiated thyroid cancer (dmDTC). However, many patients fail to achieve satisfactory effects and prognosis. Anlotinib is a highly effective antiangiogenic tyrosine kinase inhibitor (TKI) that has shown promisin...

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Main Authors: Yan Li, Jianjing Liu, Qian Su, Xueyao Liu, Zhen Yang, Zhao Yang, Jie Fu, Yan Zhang, Lina Tong, Fang Yang, Dong Dai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1622676/full
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author Yan Li
Jianjing Liu
Jianjing Liu
Qian Su
Xueyao Liu
Zhen Yang
Zhao Yang
Jie Fu
Yan Zhang
Lina Tong
Fang Yang
Dong Dai
Dong Dai
author_facet Yan Li
Jianjing Liu
Jianjing Liu
Qian Su
Xueyao Liu
Zhen Yang
Zhao Yang
Jie Fu
Yan Zhang
Lina Tong
Fang Yang
Dong Dai
Dong Dai
author_sort Yan Li
collection DOAJ
description BackgroundRadioactive iodine (RAI) is the standard treatment for distant metastatic differentiated thyroid cancer (dmDTC). However, many patients fail to achieve satisfactory effects and prognosis. Anlotinib is a highly effective antiangiogenic tyrosine kinase inhibitor (TKI) that has shown promising efficacy in RAIR-DTC patients. This study evaluated the efficacy and safety of anlotinib in combination with 131I in dmDTC.MethodsThis single-arm, phase II study was prospectively registered on the Chinese Clinical Trial Registry (ChiCTR2500095313). The key eligible criteria included patients with dmDTC who had at least one measurable metastatic lesion capable of iodine uptake and were planned to receive RAI therapy. Previous treatment with TKI was not permitted. Patients underwent a whole-body iodine scan (Rx-WBS) following iodine administration on days 3-5. When confirmed iodine uptake in metastatic lesions, anlotinib would be given at 12 mg (QD, 2 weeks on/1 week off, Q3W) initially. One combination treatment cycle consisted of 12 weeks of anlotinib and 1 dose of iodine-131. The primary endpoints were the objective response rate (ORR) and changes in thyroglobulin (Tg) levels. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety.ResultsFrom October 2022 to September 2024, 20 patients (4 males and 16 females) with distant metastatic DTC were enrolled. All patients who had completed at least one cycle of combined treatment were eligible for data analysis. The median follow-up was 13.7 months. 11 patients achieved partial response (PR), 8 patients achieved stable disease (SD), and 1 patient had progressive disease (PD). ORR and DCR were 55.0% [95% Confidence Interval (CI): 31.5%-76.9%] and 94.7% (95% CI: 75.1%-99.9%) respectively. Median PFS was not reached. All patients achieved a biochemical response according to protocol-defined criteria, defined as a ≥25% decrease in Tg levels. Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 10 (50%; most common hypertension) patients. Dose reductions of anlotinib were required in 10 (50%) patients due to AEs, and no patient discontinued treatment because of AEs. No serious adverse events (SAEs) or deaths were reported.ConclusionsThis study demonstrates the promising efficacy and safety of combining the TKI with 131I therapy, suggesting that anlotinib may be a viable option for dmDTC.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=226033, identifier ChiCTR2500095313.
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publisher Frontiers Media S.A.
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series Frontiers in Oncology
spelling doaj-art-29040dfc32344f67bbee6fbf1f73c87f2025-08-20T03:17:55ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16226761622676Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II studyYan Li0Jianjing Liu1Jianjing Liu2Qian Su3Xueyao Liu4Zhen Yang5Zhao Yang6Jie Fu7Yan Zhang8Lina Tong9Fang Yang10Dong Dai11Dong Dai12Department of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for China, Tianjin, ChinaDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for China, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for China, Tianjin, ChinaDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for China, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for China, Tianjin, ChinaBackgroundRadioactive iodine (RAI) is the standard treatment for distant metastatic differentiated thyroid cancer (dmDTC). However, many patients fail to achieve satisfactory effects and prognosis. Anlotinib is a highly effective antiangiogenic tyrosine kinase inhibitor (TKI) that has shown promising efficacy in RAIR-DTC patients. This study evaluated the efficacy and safety of anlotinib in combination with 131I in dmDTC.MethodsThis single-arm, phase II study was prospectively registered on the Chinese Clinical Trial Registry (ChiCTR2500095313). The key eligible criteria included patients with dmDTC who had at least one measurable metastatic lesion capable of iodine uptake and were planned to receive RAI therapy. Previous treatment with TKI was not permitted. Patients underwent a whole-body iodine scan (Rx-WBS) following iodine administration on days 3-5. When confirmed iodine uptake in metastatic lesions, anlotinib would be given at 12 mg (QD, 2 weeks on/1 week off, Q3W) initially. One combination treatment cycle consisted of 12 weeks of anlotinib and 1 dose of iodine-131. The primary endpoints were the objective response rate (ORR) and changes in thyroglobulin (Tg) levels. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety.ResultsFrom October 2022 to September 2024, 20 patients (4 males and 16 females) with distant metastatic DTC were enrolled. All patients who had completed at least one cycle of combined treatment were eligible for data analysis. The median follow-up was 13.7 months. 11 patients achieved partial response (PR), 8 patients achieved stable disease (SD), and 1 patient had progressive disease (PD). ORR and DCR were 55.0% [95% Confidence Interval (CI): 31.5%-76.9%] and 94.7% (95% CI: 75.1%-99.9%) respectively. Median PFS was not reached. All patients achieved a biochemical response according to protocol-defined criteria, defined as a ≥25% decrease in Tg levels. Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 10 (50%; most common hypertension) patients. Dose reductions of anlotinib were required in 10 (50%) patients due to AEs, and no patient discontinued treatment because of AEs. No serious adverse events (SAEs) or deaths were reported.ConclusionsThis study demonstrates the promising efficacy and safety of combining the TKI with 131I therapy, suggesting that anlotinib may be a viable option for dmDTC.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=226033, identifier ChiCTR2500095313.https://www.frontiersin.org/articles/10.3389/fonc.2025.1622676/fullanlotinib131I therapydistant metastatic differentiated thyroid cancerefficacysafety
spellingShingle Yan Li
Jianjing Liu
Jianjing Liu
Qian Su
Xueyao Liu
Zhen Yang
Zhao Yang
Jie Fu
Yan Zhang
Lina Tong
Fang Yang
Dong Dai
Dong Dai
Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study
Frontiers in Oncology
anlotinib
131I therapy
distant metastatic differentiated thyroid cancer
efficacy
safety
title Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study
title_full Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study
title_fullStr Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study
title_full_unstemmed Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study
title_short Efficacy and safety of anlotinib in combination with ¹³¹I therapy in the treatment of distant metastatic differentiated thyroid cancer: a single-arm, phase II study
title_sort efficacy and safety of anlotinib in combination with ¹³¹i therapy in the treatment of distant metastatic differentiated thyroid cancer a single arm phase ii study
topic anlotinib
131I therapy
distant metastatic differentiated thyroid cancer
efficacy
safety
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1622676/full
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