Abstract
Background: Meta-analyses aimed to assess the effectiveness and safety of targeted and contemporary therapies utilised in locally advanced and metastatic anaplastic thyroid cancer (ATC). Methods: Employing PRISMA and MOOSE guidelines, PubMed, Scopus, Cochrane Library and Web of Science were explored from the inception of targeted therapy until December 2024. A meta-analysis was performed to evaluate the effectiveness, toxicity and survival outcomes of various mutationally directed agents, chemotherapy and radiotherapy in locally advanced/metastatic ATC cases. Results: A total of 47 studies (26 prospective phase II trials and 21 retrospective studies) involving 980 patients met the inclusion criteria. The pooled results showed an overall response rate (ORR) of 29.7% (95% CI: 25.4-34.2%; I(2) = 42.4%; p < 0.0001). A total of 49.9% deaths were reported, although a significant number remained alive compared to baseline (mean difference [MD]: 2.07, 95% CI: 1.90-2.24; I(2) = 88.6%; p < 0.0001). The pooled median progression-free survival (PFS) was 5.4 months (95% CI: 4.0-6.7 months; I(2) = 97.9%; p < 0.0001). Dabrafenib/trametinib (DT) with and without pembrolizumab and lenvatinib plus pembrolizumab (LP) were associated with higher ORR rates and improved OS and PFS. About 51.% of studies mentioned bio-marker analysis (BRAFV600 [14.7%], PDL1 [9.2%], RAS [1.1%], PIK3CA [1.0%] and NTRK1/3 [0.7%]). Toxicity was reported in 94.7% of patients. Conclusions: This meta-analysis found that DT could be a promising first-line treatment option for BRAFV600-mutated ATC, with or without immunotherapy. Alternatively, LP shows potential in BRAFV600 wild-type and PDL1-overexpressing cases. Routine biomarker analysis remains critical for optimising ATC management strategies.