Locally advanced or metastatic thyroid cancer treated with donafenib with or without chemotherapy: A real-world study.

Abstract

e18019 Background: Neoadjuvant therapy is often required for patients (pts) with locally advanced thyroid cancer (LATC). Our prior research demonstrated that anlotinib combined with chemotherapy exhibited favorable efficacy and safety as a first-line treatment for anaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid. Donafenib, another small-molecule, multi-targeted tyrosine kinase inhibitor, has shown significant clinical benefit in patients with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). This study aims to evaluate the efficacy and safety of donafenib alone or in combination with chemotherapy in patients with LATC or metastatic thyroid cancer (TC). Methods: This real-world, observational study included pts with LATC or metastatic TC who received either donafenib monotherapy or donafenib in combination with chemotherapy at the Department of Head-Neck and Thyroid Surgery, The First Affiliated Hospital of USTC, between June 1, 2024, and October 25, 2025. All enrolled pts underwent multidisciplinary team (MDT) evaluation before treatment initiation. Donafenib plus chemotherapy was considered in cases of high tumor burden (e.g., causing dyspnea) or in patients who had previously received combination chemotherapy. The primary endpoint was objective response rate (ORR). Secondary endpoints included R0/R1 resection rate, progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and treatment-related adverse events (TRAEs). Tumor responses were assessed according to RECIST v1.1 criteria. Results: Among the 15 patients analyzed, 12 had DTC and 3 had ATC. The median age was 70 years (range, 30.0–76.0). 40% (6/15) had undergone prior surgery, and 33.3% (5/15) had previously received radioiodine (iodine-131) therapy. 86.7%(13/15) of pts had stage IV disease (other 2 pts were in stage I becease of age under 55) . As of data cutoff (December 30, 2025), the median follow-up duration was 8.73 months. Based on RECIST 1.1, the best ORR was 20%, and the DCR was 93.3% ( 3 pts with partial responses, 11 pts with stable disease [SD] ). Notably, target lesions in 6 SD pts shrank by 21.1%–27.4%. Of the 13 pts with locally advanced thyroid cancer (LATC), 5 underwent subsequent surgery, and 80% (4/5) achieved R0/R1 resection. Among pts who did not undergo surgery, median PFS had not yet been reached. The 6-month PFS rate was 88.9%. TRAEs occurred in 66.7% (10/15) of pts. Grade ≥3 TRAEs were observed in 2 pts (13.3%). No treatment-related deaths were reported. Conclusions: This real-world study suggests that donafenib either as monotherapy or in combination with chemotherapy is both effective and well-tolerated in patients with locally advanced or metastatic thyroid cancer.