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Efficacy of Selpercatinib in RET -Altered Thyroid Cancers
Journal article   Open access   Peer reviewed

Efficacy of Selpercatinib in RET -Altered Thyroid Cancers

Lori J Wirth, Eric Sherman, Bruce Robinson, Benjamin Solomon, Hyunseok Kang, Jochen Lorch, Francis Worden, Marcia Brose, Jyoti Patel, Sophie Leboulleux, …
The New England journal of medicine, Vol.383(9), pp.825-835
08/27/2020
DOI: 10.1056/nejmoa2005651
PMCID: PMC10777663
PMID: 32846061
url
https://doi.org/10.1056/nejmoa2005651View
Published (Version of record) Open Access

Abstract

mutations occur in 70% of medullary thyroid cancers, and fusions occur rarely in other thyroid cancers. In patients with -altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown. We enrolled patients with -mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response), as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety. In the first 55 consecutively enrolled patients with -mutant medullary thyroid cancer who had previously received vandetanib, cabozantinib, or both, the percentage who had a response was 69% (95% confidence interval [CI], 55 to 81), and 1-year progression-free survival was 82% (95% CI, 69 to 90). In 88 patients with -mutant medullary thyroid cancer who had not previously received vandetanib or cabozantinib, the percentage who had a response was 73% (95% CI, 62 to 82), and 1-year progression-free survival was 92% (95% CI, 82 to 97). In 19 patients with previously treated fusion-positive thyroid cancer, the percentage who had a response was 79% (95% CI, 54 to 94), and 1-year progression-free survival was 64% (95% CI, 37 to 82). The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), increased alanine aminotransferase level (in 11%), increased aspartate aminotransferase level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Of all 531 patients treated, 12 (2%) discontinued selpercatinib owing to drug-related adverse events. In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).
 Adolescent Adult Aged Aged, 80 and over Female Humans Hypertension - chemically induced Intention to Treat Analysis Kaplan-Meier Estimate Male Middle Aged Mutation Progression-Free Survival Protein Kinase Inhibitors - administration & dosage Protein Kinase Inhibitors - adverse effects Proto-Oncogene Proteins c-ret - analysis Proto-Oncogene Proteins c-ret - antagonists & inhibitors Proto-Oncogene Proteins c-ret - genetics Pyrazoles - administration & dosage Pyrazoles - adverse effects Pyridines - administration & dosage Pyridines - adverse effects Thyroid Neoplasms - drug therapy Transaminases - blood Treatment Outcome Young Adult

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