Tyrosine kinase inhibitors for radioiodine refractory differentiated thyroid cancer: A systematic review and meta-analysis

Clin Endocrinol (Oxf). 2024 Apr;100(4):379-388. doi: 10.1111/cen.15027. Epub 2024 Feb 13.


Background: The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs) in radioiodine refractory differentiated thyroid cancer (RAIR-DTC). However, the available evidence cannot determine the optimal choice of TKI in RAIR-DTC.

Methods: This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT) of RAIR-DTC patients treated with the TKI system. Outcomes, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were reported.

Results: Seven studies involving 1310 patients with RAIR-DTC was conducted to compare the PFS and OS of various TKI monotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR] 0.19, 95% credible interval [CrI] 0.14-0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18-0.97) and anlotinib (HR 0.36, 95% CrI 0.18-0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR-DTC, although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR-DTC patients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment.

Conclusions: The results of this meta-analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine-refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR-DTC. This study is beneficial for formulating patients' treatment plans and guides clinicians' decision-making.

Keywords: differentiated thyroid cancer; meta-analysis; systematic review; tyrosine kinase inhibitors.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Iodine Radioisotopes / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Quinolines*
  • Thyroid Neoplasms* / pathology
  • Tyrosine Kinase Inhibitors


  • Antineoplastic Agents
  • Iodine Radioisotopes
  • lenvatinib
  • Phenylurea Compounds
  • Quinolines
  • Tyrosine Kinase Inhibitors