Endocrine Abstracts

Background: RET proto-oncogene that encodes receptor tyrosine kinase is responsible for the pathogenesis of most of the thyroid cancer subtypes. Selpercatinib and pralsetinib, both specific RET-kinase inhibitors, are the only two FDA-approved drugs for RET-altered thyroid cancer. We aimed to evaluate the safety and efficacy of these two drugs.

Methods: We searched PubMed, Embase, Cochrane and Clinicaltrials.gov databases for RCTs and observational studies published up to March 28, 2024 and included the ones that saw the efficacy of RET-kinase inhibitors in RET-altered thyroid cancer and reported any one of the desired endpoints. The primary endpoint was 1-year progression free survival (PFS) and objective response rate (ORR). The quantitative analyses were done using R programming language. Heterogeneity was examined with I ² test.

Results: We included 4 studies with 560 patients, of them, 510 had RET-mutant and 50 had RET-fusion thyroid cancer. The 1-year PFS was 0.84 (95% CI=0.79-0.88, I^2=43%), ORR was 0.69 (95% CI=0.65-0.73, I^2=0), progressive disease was 0.02 (95% CI=0.01-0.03, I^2=0), stable disease was 0.24 (95% CI=0.20-0.29, I^2=39%). Some important adverse events were hypertension 0.35 (95% CI=0.29-0.42, I^2=53%), diarrhoea 0.20 (95% CI=0.15-0.26, I^2=56%), increased ALT 0.28 (95% CI=0.24-0.32, I^2=23%), increased AST 0.32 (95% CI=0.23-0.41, I^2=78%), Electrocardiogram QT prolongation 0.14 (95% CI=0.11-0.18, I^2=0).

Conclusion: These findings suggest that selpercatinib and pralsetinib are efficacious and safe to use in RET-altered thyroid cancer. However, more randomized trials are needed to prove our findings.