Efficacy of Selpercatinib in RET-Altered Thyroid Cancers

By L. Wirth, E. Sherman, B. Robinson, B. Solomon, Hyunseok Kang, J. Lorch, F. Worden, M. Brose, J. Patel, S. Leboulleux and 31 more. New England Journal of Medicine, 2020

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BACKGROUND RET mutations occur in 70% of medullary thyroid cancers and RET fusions rarely in other thyroid cancers. We evaluated the efficacy and safety of selpercatinib, a selective RET inhibitor, in patients with advanced RET-altered thyroid cancers. METHODS Patients with RET-mutant medullary thyroid cancer with and without prior vandetanib or cabozantinib treatment, as well as previously treated RET fusion-positive thyroid cancers, were enrolled in a first-in-human, phase 1/2 trial of selpercatinib. The primary endpoint was objective response rate by independent review committee. Secondary endpoints included duration of response, progression-free survival, and safety. RESULTS In the first 55 consecutively enrolled RET-mutant medullary thyroid cancer patients previously treated with vandetanib and/or cabozantinib, the response rate was 69% (95% CI,55 to 81) and 1-year progression-free survival rate 82% (95% CI: 69–90). In 88 patients with RET-mutant vandetanib and cabozantinib-naïve medullary thyroid cancer, the response rate was 73% (95% CI, 62–82) and 1-year progression-free survival rate 92% (95% CI: 82–97). In 19 patients with previously-treated RET fusion-positive thyroid cancer, the response rate was 79% (95% CI, 54–94). The most common grade ≥3 adverse events were hypertension (21%), increased alanine aminotransferase (11%), increased aspartate aminotransferase (9%), hyponatremia (8%), and diarrhea (6%). Four patients (3%) discontinued selpercatinib due to drug-related adverse events. CONCLUSIONS In this phase 1/2 trial, selpercatinib demonstrated durable efficacy with mainly low-grade toxicity in medullary thyroid cancer patients with and without prior vandetanib or cabozantinib treatment, and promising activity in RET fusion-positive thyroid cancer.

Subfields: Cancer Research, Endocrinology, Diabetes and Metabolism

View Paper: https://www.semanticscholar.org/paper/840c34bc93fcc88684be3f232a73f3d54bb08830

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