Long-Term Clinical Outcomes of Patients with Differentiated Thyroid Cancer Treated with Lenvatinib: Results from Real-World Practice in Japan

Background: Although accumulated experience with lenvatinib in patients with differentiated thyroid cancer (DTC) and progressive radioactive iodine (RAI)-refractory disease has been used to improve management strategies for this disease, findings regarding the actual clinical picture and long-term observation data are insufficient. Methods: We conducted a retrospective cohort study of patients with DTC who received lenvatinib treatment from 2011 to 2022 at the National Cancer Center Hospital East, Japan. The patients were treated under the following treatment and management policies (1) starting dose at 24 mg/day, (2) schedule modification according to individual adverse events status (planned drug holidays), (3) dose escalation of lenvatinib, and (4) local therapy at disease progression, if applicable. This is a retrospective cohort study, although some patients were enrolled in a prospective clinical trial (NCT01321554 and UMIN000022243). Results: Of 91 patients, 59 (64.8%) had papillary carcinoma and 22 (24.2%) had follicular carcinoma. Best overall response in all patients was 60.4% (partial response in 55 and complete response in 0). With a median observation period of 2.9 years (range, 0.1-12.4; interquartile range, 1.7-4.6) under supportive management, including the planned drug holidays (n = 72, 79.1%), dose escalation of lenvatinib at systemic disease progression (n = 21, 23.1%), and local therapy for oligoprogressive disease (n = 11, 12.1%), median progression-free survival and overall survival were 2.4 years (95% confidence interval [CI] 1.9-3.3) and 5.1 years (95% CI 3.3-6.7), respectively. At the time of data cutoff, 19.8% had discontinued lenvatinib treatment due to adverse events, although no adverse event was grade 5. Conclusions: In patients with RAI-refractory DTC treated with lenvatinib, careful treatment optimization and management of adverse events contribute to a favorable, durable prognosis.