Efficacy and Safety of Lenvatinib for Neoadjuvant Therapy in Patients with Locally Advanced Thyroid Cancer: A Real-world Prospective Study

Background Surgical resection is the cornerstone of treatment for thyroid cancer. However, some patients have locally advanced disease at first diagnosis and are therefore ineligible for radical resection. Neoadjuvant therapy is a treatment option for some patients. Lenvatinib, a multi-target kinase inhibitor with antiangiogenic activity, has been approved for differentiated thyroid cancer. We here evaluated the safety and efficacy of lenvatinib as neoadjuvant therapy for locally advanced differentiated thyroid cancer. Methods In this single-arm, real-world trial, patients with locally advanced differentiated thyroid cancer and at least one measurable target lesion received lenvatinib 24 mg once daily for at least 8 weeks. The primary endpoint was the objective response rate as per RECIST v1.1. Additional endpoints included the disease control rate, R0/1 resection rate, and safety. Results Twelve patients with locally advanced differentiated thyroid cancer received lenvatinib for a median of 8 weeks (range, 4–32 weeks). The objective response and disease control rates were 33.3% (95% confidence interval = 11.3%–64.6%) and 91.7%, respectively. Three patients did not undergo surgery because of tumor progression and their refusal; R0/1 resection was achieved in eight of the nine remaining patients (88.9%). The commonest drug-related adverse events were hypertension (41.7%), diarrhea (41.7%), and fatigue (33.3%). There were no major treatment-related perforation events or Grade 5 treatment-related adverse events. Conclusions The preliminary analysis shows lenvatinib as neoadjuvant treatment has an acceptable efficacy and safety and a relatively high R0/1 resection rate. Further prospective studies investigating combination therapies and identifying appropriate patient cohorts are warranted.