Efficacy and Safety of Multikinase Inhibitors for Patients With Refractory Thyroid Cancer: Systematic Review and Network Meta-Analysis

Abstract Context Multikinase inhibitors (MKIs) improve the treatment of refractory thyroid cancer, including radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and advanced medullary thyroid carcinoma (aMTC). Objective This study aims to compare the efficacy of MKIs in improving survival outcomes and safety. Data Sources Comprehensive database searches of MEDLINE via PubMed, EMBASE, and Cochrane were performed from inception to December 2023. Study Selection Three independent authors selected these studies. Randomized controlled trials that compared the use of a MKI to other MKIs or placebo were included. Data Extraction and Synthesis This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Risk of bias was analyzed using the Cochrane risk of bias 2 tool. Bayesian network meta-analysis was performed. Treatments were grouped into common nodes based on the type of MKI. Main Outcomes and Measures Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate, disease control rate, clinical benefit rate, and adverse events. Results Cabozantinib 60 mg/day (CAB60) was associated with the highest prolonged PFS in RAIR-DTC patients, followed by lentivatinib 18 or 24 mg/day (LEN18 or LEN24), and apatinib. PFS was also improved in aMTC patients who received CAB 140 mg/day (CAB140), CAB60, or anlotinib. A significantly greater improvement on the performance of OS was seen in CAB60, LEN24, anlotinib, and sorafenib in RAIR-DTC patients, but in aMTC patients there were lack of statistical differences. Compared with the low-dose MKIs, high-dose MKIs such as CAB, LEN, and vandetanib increased the incidence of adverse events. Conclusion CAB60, LEN, and apatinib are promising topical MKIs with statistically significant primary outcomes in RAIR-DTC patients, while CAB and anlotinib are effective in prolonging PFS in aMTC patients.