Lenvatinib for Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma and Candidate Biomarkers Associated with Survival: A Multicenter Study in Korea

Background: Lenvatinib, an oral multikinase inhibitor, is the latest addition to the treatment options for radioactive iodine (RAI)-refractory progressive differentiated thyroid carcinoma (DTC). This study investigated the efficacy of lenvatinib in real-world practice and prognostic biomarkers of survival. Methods: This multicenter study included 43 patients receiving lenvatinib as first-line or second-line treatment after sorafenib for RAI-refractory DTC. Progression-free survival (PFS) was evaluated according to various clinical factors including thyroglobulin doubling time (TgDT), tumor volume DT (TVDT), and tumor growth slope (TGS; slope of tumor change rate). Results: Patients were treated with lenvatinib for a median of 14 months; 32 were previously treated with sorafenib. The median follow-up from lenvatinib initiation to the last censoring or death was 16 months. The median starting dose of 20 mg was reduced to a median sustainable dose of 10 mg in accordance with patient adverse events (AEs). The median PFS was 21.8 months; the median overall survival was not reached. The disease control rate was 97.7%, with the first objective response at 3.8 months. PFS was not significantly associated with previous sorafenib treatment, metastatic sites, or sustainable dose. TGS measured before (TGS(pre), p = 0.003) and after (TGS(post), p = 0.036) the initiation of lenvatinib was associated with PFS. The sum of the largest diameters of target lesions (p = 0.043) and TgDT (p = 0.024) were associated with PFS, but TVDT calculated before (TVDTpre, p = 0.923) or after (TVDTpost, p = 0.966) lenvatinib treatment did not impact PFS. Lenvatinib was withdrawn in 24 patients (55.8%): in 6 patients because of treatment-induced AEs and in 18 patients because of disease progression or poor performance status. AEs of any grade were reported in all patients, and grade 3-4 AEs in 23.2% of the patients. The most frequent AE was fatigue or asthenia. Conclusions: Our results indicate that reduced doses of lenvatinib triggered by emergent AEs did not abrogate its apparent efficacy in patients with RAI-refractory DTCs. Rather, the sustained use of reduced doses of lenvatinib with a low rate of severe AEs may have contributed to the favorable outcomes. TgDT and TGS can assist in predicting the outcomes in these patients.