Clinical efficacy of lenvatinib for the treatment of radioiodine-refractory thyroid carcinoma: a systematic review and meta-analysis of clinical trials.

OBJECTIVE To evaluate the efficacy of lenvatinib in the treatment of Radioiodine-refractory thyroid carcinoma. BACKGROUND Thyroid carcinoma is one of the top ten carcinoma worldwide. Clinically, thyroid cancers are managed with resections and adjuvant therapy with radioiodine. However, radioiodine is not effective for radioiodine-refractory (RR) thyroid carcinoma in some patients. Lenvatinib is a multi-kinase inhibitor for treatment of RR-thyroid carcinoma. Several clinical trials showed its efficacy in prolonging progression-free survival (PFS) and overall survival (OS). DESIGN, PATIENTS AND MEASUREMENTS A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 8 June 2020. Search keywords were lenvatinib, thyroid carcinoma, randomised controlled trials. Clinical trials fulfilling the SELECT protocol were selected to evaluate the efficacy of lenvatinib in terms of prolongation of PFS, OS and objective response rate (ORR). The risk ratio and distribution of grade 3 or above adverse events were documented. RESULTS Of the 3997 patients of mean age 62.5 years in fifteen selected studies, lenvatinib is associated with prolonged PFS (hazard ratio 0.24, 95% CI, 0.19-0.31, p<0.001) and OS (hazard ratio 0.65, 95% CI, 0.52-0.81, p<0.001). Compared with placebo, the risk ratio of ORR and incidence of grade-3 or above adverse events are 35.41 (95% CI, 19.42-64.58, p<0.001) and 8.25 (95% CI, 6.50-10.46, p<0.001), respectively. Subgroup analysis shows that lenvatinib is effective for all patients with RR-thyroid carcinoma, regardless of age, histological subtypes, radiological subtypes and mutation status. CONCLUSION Lenvatinib is effective in treatment of RR-thyroid carcinoma. Close monitoring of serious adverse events is recommended.