Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study

Background: Sorafenib and lenvatinib have been widely adopted to treat radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). However, limited data exist regarding a direct comparison of these tyrosine kinase inhibitors (TKIs). We aimed to evaluate the clinical efficacy and safety of two TKIs as first-line therapy in patients with distant metastatic or locally advanced, progressive, RAI-refractory DTC in real-world practice. Methods: In this multicenter, retrospective cohort study, we evaluated 136 patients with progressive distant metastatic or locally advanced, progressive, RAI-refractory DTC or poorly differentiated thyroid carcinoma (PDTC) who received first-line sorafenib or lenvatinib treatment. The primary outcome was progression-free survival (PFS). We also evaluated the objective response rate, disease-control rate, clinical benefit rate, and safety. Results: The median age of the patients was 68 years, and 35% (47/136) were male. Eighty and fifty-six patients were included in the sorafenib and lenvatinib groups, respectively. The median PFS was 13.3 months [95% confidence interval, CI, 9.9-18.1 months] in the sorafenib group and 35.3 months [CI, 18.2 months to upper limit not reported as the median was not reached] in the lenvatinib group (p = 0.001). A significantly prolonged PFS was observed in the lenvatinib group (compared with the sorafenib group) after adjusting for age, sex, pathology, disease-related symptom, lung-only metastasis, cumulative RAI dose, time from diagnosis, treatment duration, and longest diameter of the target lesion (hazard ratio = 0.34, CI, 0.19-0.60, p < 0.001). The partial response rate was 24% and 59% in the sorafenib and lenvatinib groups, respectively (p < 0.001). More common grade 3-4 adverse events were hypertension (16%, 9/56 vs. 1%, 1/80, p = 0.002) and proteinuria (32%, 18/56 vs. 0%, p < 0.001) in the lenvatinib group, and hand-foot skin reaction (24%, 19/80 vs. 4%, 2/56, p = 0.001) in the sorafenib group. Conclusion: In our study of Asian patients, first-line lenvatinib treatment of metastatic or locally advanced, progressive, RAI-refractory DTC or PDTC was associated with a longer PFS compared with sorafenib. However, severe hypertension and proteinuria were observed more frequently after lenvatinib treatment than after sorafenib treatment.