Efficacy of Selpercatinib in RET-Altered Thyroid Cancers

This phase 1–2 trial evaluated the efficacy and safety of selpercatinib, a selective RET kinase inhibitor, in patients with RET-altered thyroid cancers. The study included 162 patients across three cohorts: RET-mutant medullary thyroid cancer (MTC) previously treated with vandetanib/cabozantinib (n=55), RET mutant MTC without prior vandetanib/cabozantinib (n=88), and RET fusion-positive thyroid cancer (n=19). The primary endpoint was objective response rate (ORR) assessed by independent review. Results showed ORRs of 69% (95% CI: 55–81) in pretreated MTC, 73% (62–82) in treatment naive MTC, and 79% (54–94) in RET fusion positive thyroid cancer. One year progression-free survival rates were 82%, 92%, and 64%, respectively. Common grade 3–4 adverse events included hypertension (21%), elevated alanine aminotransferase (11%), and diarrhea (6%). Only 2% of patients discontinued treatment due to drug-related adverse events. Selpercatinib demonstrated durable efficacy with a manageable safety profile in RET-altered thyroid cancers, supporting its potential as a targeted therapy option.

This phase 1–2 trial evaluated the efficacy and safety of selpercatinib, a selective RET kinase inhibitor, in patients with RET-altered thyroid cancers. The study included 162 patients across three cohorts: RET-mutant medullary thyroid cancer (MTC) previously treated with vandetanib/cabozantinib (n=55), RET mutant MTC without prior vandetanib/cabozantinib (n=88), and RET fusion-positive thyroid cancer (n=19). The primary endpoint was objective response rate (ORR) assessed by independent review. Results showed ORRs of 69% (95% CI: 55–81) in pretreated MTC, 73% (62–82) in treatment naive MTC, and 79% (54–94) in RET fusion positive thyroid cancer. One year progression-free survival rates were 82%, 92%, and 64%, respectively. Common grade 3–4 adverse events included hypertension (21%), elevated alanine aminotransferase (11%), and diarrhea (6%). Only 2% of patients discontinued treatment due to drug-related adverse events. Selpercatinib demonstrated durable efficacy with a manageable safety profile in RET-altered thyroid cancers, supporting its potential as a targeted therapy option.