Efficacy and safety of anlotinib in neoadjuvant treatment of locally advanced differentiated thyroid cancer (DTC): A multicenter, single-arm, phase II study.

6096 Background: Neoadjuvant therapy is often necessary for patients with locally advanced inoperable or locally recurrent thyroid cancer without chance of surgery. Anlotinib is a small molecule multi-targeted tyrosine kinase inhibitor that can inhibit tumor angiogenesis while simultaneously inhibiting tumor growth, and has demonstrated significant benefit in radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). Our study aims to evaluate the efficacy and safety of anlotinib in the preoperative neoadjuvant therapy with unresectable DTC. Methods: The study (ChiCTR2100048077) was a single-arm, open-label, multicenter phase II study. Eligible patients were between 18-75 years old with histopathological confirmed locally advanced differentiated thyroid cancer at high surgical risk and susceptible to postoperative recurrence. Patients with locally advanced DTC with distant metastasis and potential for local resection were also included. Patients received 12mg of anlotinib once daily on a schedule of 2 weeks on and 1 week off until surgery or disease progression and treatment discontinuation. The primary endpoint was objective response rate (ORR). The secondary endpoints included time to response (TTR), disease control rate (DCR), actual surgery rate, rate of R0 resection and safety. The objective response was evaluated according to RECIST 1.1. Here we report the results of this study. Results: 50 patients (20 males vs. 30 females) were enrolled from 3/2022 to 12/2023, with a median age was 56.5 (range: 26.0-74.0), 52% of patients had undergone previous surgery and 14% of patients had received radioiodine (iodine-131) treatment. At the cutoff date (November 30th, 2024), out of 43 patients with assessable efficacy, no CR occurred, 18 patients achieved PR, 24 patients achieved SD and 1 patients had PD.ORR and DCR was 41.86% (95%CI:27.01-57.87) and 97.67% (95%CI: 87.71-99.94) respectively. 21 patients underwent surgery, 57.1% (12/21) achieved R0 resection. Median time to response was 2.84 months (range: 1.31-5.16 months). In patients who did not undergo surgical treatment, the median progression-free survival (mPFS) had not yet reached. The 6-month progression-free survival rate (PFS rate) was 95.83% (95%CI:73.92-99.40). 76%(38/50) of patients had experienced anlotinib treatment-related adverse events (TRAEs), Grade 3+ TRAEs were observed in 9 patients (18%, most common hypertension). 16% (8/50) of patients were discontinued due to TRAEs. No deaths attributable to adverse events (AEs) were observed. Conclusions: The study indicated that anlotinib was safe and effective as a neoadjuvant therapy for patients with locally advanced DTC. Clinical trial information: ChiCTR2100048077 .