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

Abstract

e18133 Background: Distant metastatic differentiated thyroid cancer (DTC) commonly responds poorly to radioiodine ( 131 I) treatment alone. Anlotinib is a multi-targeted tyrosine kinase inhibitor(TKI) that can inhibit tumor angiogenesis while simultaneously inhibiting tumor growth, and has exerted promising antitumor activity in multiple advanced solid tumors. This study aimed to evaluate the efficacy and safety of combined treatment with Anlotinib hydrochloride capsules and 131 I in distant metastatic DTC. Methods: This is a single-arm, phase II clinical trial (ChiCTR2500095313). The key eligibility criteria included patients with distant metastatic DTC who had at least one measurable metastatic lesion capable of iodine uptake and were planned to receive radioactive iodine (RAI) therapy. Previous treatment with TKIs were not permitted. Patients underwent a whole-body iodine scan (Rx-WBS) on days 3-5 following iodine administration. Upon confirmation of iodine uptake in metastatic lesions, anlotinib therapy was initiated, with each treatment cycle consisting of 12 weeks of combined anlotinib and iodine-131 therapy. Patients initially received anlotinib at a dose of 12 mg ( QD, 2 weeks on/1week off , Q3W). The primary endpoints were the objective response rate (ORR) and change of thyroglobulin (Tg) levels. The secondary endpoints included disease control rate (DCR), median progression-free survival (mPFS) and safety. Results: From October 2022 to January 2025, a total of 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. Median follow-up time was 13.7m. No CR occurred, 11 patients achieved PR, 8 patients achieved SD and 1 patient had PD. ORR and DCR were 55.0% (95%CI, 31.5-76.9) and 94.7% (95%CI, 75.1-99.9) respectively. Median PFS was not reached at the time of analysis. After completing a full treatment cycle, all patients were observed to have achieved biochemical remission, defined as a decrease in Tg levels of ≥25%. Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 10(50%，most common hypertension) patients. Dose reductions of anlotinib were necessitated in 10(50%) patients due to AEs, and no patient discontinued treatment as a result of AEs. No serious adverse events (SAEs) or deaths were reported. Conclusions: This study demonstrates the favorable efficacy and safety of combining the TKI with iodine-131 therapy, suggesting that anlotinib may be a viable option for the treatment of distant metastatic DTC. We look forward to future large-scale randomized clinical trials to further evaluate the efficacy and safety of anlotinib combined with iodine-131 in the treatment of DTC. Clinical trial information: ChiCTR2500095313 .