Sequential Therapy with Anlotinib and Radioiodine for Distant Metastatic Differentiated Thyroid Cancer: A Phase II Clinical Trial
Hongjun Song, Chentian Shen, Youben Fan, Zhiyan Liu, Yonggang Wang, Quanyong Luo, Libo ChenAbstract
Background
Radioiodine (RAI) alone exhibited limited efficacy in distant metastatic differentiated thyroid cancer (DTC). We hypothesized that pretreatment with anlotinib, a potent antiangiogenic tyrosine kinase inhibitor, would reduce tumor burden and improve therapeutic response.
Methods
This prospective, single-arm phase II trial enrolled patients with measurable distant metastatic DTC. All patients received anlotinib 12 mg/day orally for 12 weeks. After confirmation of RAI-avid target lesions on diagnostic ¹³¹I-WBS, patients were treated with 7.4 GBq RAI and followed up for another 12 weeks. Sequential therapy continued until no effect of RAI could be anticipated. Primary endpoints were objective response rate (ORR) and safety. Registered with the Chinese Clinical Trial Registry (ChiCTR2100045178; https://www.chictr.org.cn).
Results
24 patients were enrolled. 14 (58%) were excluded due to non-RAI-avid target lesions; 10 (42%) with RAI-avid lesions received sequential therapy (median, 4.5 cycles). ORR was 60% (all partial responses), disease control rate 100%. With median follow-up 34.5 months, no disease progression or death occurred. In the subgroup of eight patients with bone target lesions, ORR was 50%. Grade 3 anlotinib-related adverse events occurred in 30% of patients; no grade 4/5 toxicities or grade ≥2 RAI-related events were observed.
Conclusion
Sequential anlotinib followed by RAI therapy demonstrated promising antitumor activity (ORR 60%) and favorable safety in RAI-avid distant metastatic DTC, particularly in bone metastases. These findings are hypothesis-generating and require validation in a randomized trial with an RAI monotherapy control arm.