Efficacy and safety of RET-kinase inhibitors in RET-altered thyroid cancers: a systematic review and single-arm meta-analysis.

Abstract

The RET proto-oncogene, which encodes a receptor tyrosine kinase, is an important factor in the pathogenesis of medullary and papillary thyroid cancers. Selpercatinib and pralsetinib, both specific RET-kinase inhibitors, are the only FDA-approved drugs for treating RET-altered thyroid cancer. We wanted to evaluate the safety and efficacy of selpercatinib and pralsetinib in RET-altered thyroid cancers. We searched the PubMed, Embase, Cochrane, and Clinicaltrials.gov databases for randomized controlled trials and observational studies published up to March 30, 2024, and included those that reported any of the desired endpoints. The primary endpoints were 1-year progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Quantitative analyses were performed using the R programming language. We included four studies with 560 patients, 510 with RET-mutant and 50 with RET-fusion thyroid cancer. The 1-year PFS was 84% (95% CI, 79-88, I 2 = 43%), ORR was 69% (95% CI, 65-73, I 2 = 0) and DCR was 93% (95% CI, 89-96, I 2 = 44%). Some important grade ≥3 adverse events were hypertension (16%; 95% CI, 11-22; I 2 = 43%), diarrhea (3%; 95% CI, 2-5; I 2 = 0), increased ALT (11%; 95% CI, 8-14; I 2 = 0) and increased AST (6%; 95% CI, 4-10; I 2 = 0). In conclusion, these findings suggest that selpercatinib and pralsetinib are efficacious and safe for use in patients with RET-altered thyroid cancer.