Manisha H Shah, MD of The James Ohio State University Comprehensive Cancer Center discusses the Efficacy of Selpercatinib in RET-Altered Thyroid Cancers.
BACKGROUND
RET mutations occur in 70 percent of cancers of the medullary thyroid and RET fusions seldom occur in other thyroid cancers. The effectiveness and safety of the selective RET inhibition is uncertain in patients with RET-altered thyroid cancers.
FOR METHODS
In a phase 1-2 trial of selpercatinib, patients with RET-mutant medullary thyroid cancer with or without prior treatment with vandetanib or cabozantinib, as well as those with previously treated RET fusion-positive thyroid cancer, were enrolled. As decided by an independent review committee, the primary endpoint was an objective response (a full or partial response). Secondary endpoints covered response length, progression-free survival, and protection.
OUTCOMES
The percentage reacting to the first 55 consecutive RET-mutant medullary thyroid cancer patients who had previously obtained vandetanib, cabozantinib, or both 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 RET-mutant medullary thyroid cancer who had not previously received vandetanib or cabozantinib, the response rate was 73 percent (95 percent CI, 62 to 82), and 92 percent (95 percent CI, 82 to 97) was 1-year progression-free survival. In 19 patients with previously treated RET fusion-positive thyroid cancer, the percentage of respondents was 79 percent (95 percent CI, 54 to 94), and 64 percent (95 percent CI, 37 to 82) was progression-free survival in 1 year. Hypertension (in 21 percent of patients), increased levels of alanine aminotransferase (in 11 percent), increased levels of aspartate aminotransferase (in 9 percent), hyponatremia (in 8 percent), and diarrhea (in 6 percent) were the most common adverse outcomes of grade 3 or greater. Of all 531 patients treated, 12 (2%) stopped selpercatinib due to adverse reactions associated with the medication.
CONCLUSIONS
In this phase 1"“2 trial, in patients with medullary thyroid cancer with and without prior treatment with vandetanib or cabozantinib, selfpercatinib demonstrated enduring efficacy with mainly low-grade toxic effects. (Funded by Loxo Oncology and others; opens in new tab) LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.
https://www.nejm.org/doi/pdf/10.1056/NEJMoa2005651