BRAF/MEK inhibitors for redifferentiation in patients with radioiodine refractory thyroid cancer: A systematic review and Meta-Analysis.

PURPOSE: Radioiodine-refractory differentiated thyroid cancer has a poor prognosis with impaired radioiodine uptake. Previous studies have demonstrated that redifferentiation therapy might restore radioiodine avidity. This study aimed to assess the efficacy and safety of redifferentiation therapy in patients with radioiodine-refractory differentiated thyroid cancer. METHODS: Relevant studies from three databases were systematically searched until March 25, 2025. The methodological quality and risk of bias were assessed using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) assessment tool. A meta-analysis was performed with Stata version 18. The study was registered in PROSPERO (CRD420251032500). RESULTS: Seven studies were included with a total of 119 evaluable patients. The pooled restoration rate of radioiodine uptake across seven studies was 0.50 (95% CI: 0.40–0.60) based on diagnostic whole-body scan. BRAF inhibitor, MEK inhibitor and combination therapy of both inhibitors demonstrated restoration rates of 0.60 (95% CI: 0.37–0.81), 0.40 (95% CI: 0.23–0.58) and 0.57 (95% CI: 0.35–0.78), respectively. The restoration rates of BRAF-mutant patients and RAS-mutant patients were 0.56 (95% CI: 0.41–0.70) and 0.70 (95% CI: 0.42–0.93), respectively. The objective response rate was 0.29 (95% CI: 0.15–0.44) and the disease control rate was 0.91 (95% CI: 0.78–0.99) from three studies that reported efficacy data for all evaluable patients. The incidence of grade 3–4 adverse events was 0.14 (95% CI: 0.01–0.34). CONCLUSION: This meta-analysis provides preliminary evidence for the efficacy and safety of BRAF/MEK-targeted redifferentiation therapy in patients with radioiodine-refractory thyroid cancer. However, evidence on its benefit in improving progression-free survival or overall survival remains scarce.