Poster Presentation ESA-SRB-APEG-NZSE 2022

The efficacy and safety of tyrosine kinase inhibitors in advanced and metastatic thyroid cancer: A systematic review and meta-analysis of Phase III randomised controlled trials (#282)

Jessica Bindra 1 2 , Stephen M Twigg 1 3 4
  1. Department of Endocrinology and Metabolism, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  2. School of Medicine, Western Sydney University, Sydney, NSW, Australia
  3. Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
  4. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Aims: To evaluate the efficacy and adverse events (AEs) of tyrosine kinase inhibitors (TKIs) in adults with advanced or metastatic thyroid cancer compared with placebo.

Methods: Database CENTRAL, OVID Medline, Embase and PubMed were searched through February 2022. We included Phase III randomised controlled trials that investigated the efficacy and AEs of TKIs in adults with advanced or metastatic thyroid cancer compared with placebo. Outcomes included objective response rate (ORR) and AEs, including diarrhoea, nausea, hypertension, proteinuria, palmar-plantar erythrodysaesthesia (PPE) and grade 3+ AEs. Pooled effect sizes were meta-analysed using RevMan 5 software through a random effects model.

Results: Six phase III RCTs (1799 patients) were included (1-6). Evaluated TKIs included lenvatinib, vandetanib, sorafenib and cabozantinib. Trials included patients with radioiodine-refractory differentiated and medullary thyroid cancer. Based on very low-certainty evidence, there was a significantly higher ORR in the TKI group compared with placebo (6 trials; 1799 participants; risk ratio (RR) 19.74, 95% CI 4.92- 79.20), mostly driven by partial response. AEs were significantly higher in the TKI group compared with placebo (diarrhoea: 6 trials; 1799 participants; RR 4.28, 95% CI 2.49-7.39; nausea: 5 trials; 1648 participants; RR 2.25, 95% CI 1.70-2.98; hypertension: 6 trials; 1799 participants; RR 4.92, 95% CI 3.53-6.85, and PPE: 5 trials; 1469 participants; RR 15.40, 95% CI 7.21-32.90). There was significantly more proteinuria with lenvatinib compared with placebo (2 trials; 543 participants; RR 12.23, 95% CI 5.61-26.68). TKIs caused significantly more grade 3+ AEs compared with placebo (6 trials; 1799 participants; RR 3.28, 95% CI 2.04-5.28).

Conclusion: This is the first systematic review on the safety and efficacy of TKIs in advanced or metastatic thyroid cancer to meta-analyse phase III RCT level data, and include the most recently published trials (4,6). This review highlights the need to balance the therapeutic effect and toxicity of TKIs.

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