Comparative efficacy and safety of tyrosine kinase inhibitors for thyroid cancer: a systematic review and meta-analysis

Endocr J. 2020 Dec 28;67(12):1215-1226. doi: 10.1507/endocrj.EJ20-0171. Epub 2020 Aug 18.


The tyrosine kinase inhibitors (TKIs) sorafenib, lenvatinib, vandetanib, and cabozantinib are currently used for thyroid cancer treatment; however, the differences in their clinical efficacy and toxicity remain unclear. This meta-analysis assessed the efficacy and toxicity of these four TKIs based on 34 studies. The pooled incidence of partial response (PR), stable disease (SD), TKI-related adverse events (AEs), and pooled median progression-free survival (PFS) were calculated with 95% confidence intervals (CI). Complete response to TKIs was extremely rare (0.3%). The highest PR rate and longest PFS were observed for lenvatinib in differentiated thyroid cancer (69%, 95% CI: 57-81 and 19 months, 95% CI: 9-29, respectively) and vandetanib in medullary thyroid cancer (40%, 95% CI: 25-56 and 31 months, 95% CI: 19-43, respectively). Although the discontinuation rate due to AEs was similar for each TKI, there was a difference in the most frequently observed AE for each TKI (hand-foot syndrome for sorafenib, hypertension and proteinuria for lenvatinib, and QTc prolongation for vandetanib). The identified differences in the TKI efficacy and AE profiles may provide a better understanding of thyroid cancer treatment. Although TKIs are promising agents for thyroid cancer treatment, they are unlikely to lead to a cure. Thus, even in the TKI era, a multimodal treatment including surgery, radioiodine therapy, external beam radiotherapy, and TKIs is required to optimize patient chances of improved survival.

Keywords: Adverse event; Meta-analysis; Thyroid cancer; Tyrosine kinase inhibitor.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use
  • Piperidines / adverse effects
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Sorafenib / adverse effects
  • Sorafenib / therapeutic use
  • Thyroid Neoplasms / drug therapy*
  • Treatment Outcome


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Piperidines
  • Protein Kinase Inhibitors
  • Quinazolines
  • Quinolines
  • Sorafenib
  • lenvatinib
  • vandetanib