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The U.S. Food and Drug Administration (FDA) has approved selpercatinib (Retevmo) for adults and children 2 years and older who have advanced thyroid cancers harboring fusion mutations involving the RET gene, require systemic therapy, and whose cancers have not responded to radioactive iodine (if eligible for this treatment).
Selpercatinib is a targeted therapy that inhibits mutant forms of the RET tyrosine kinase, a protein that is commonly mutated in several cancer types, including thyroid cancers. Portions of the RET gene sometimes fuse to other genes, resulting in the production of fusion proteins that can promote cancer growth.
Selpercatinib received accelerated approval for the same indication in adults and children 12 years and older in 2020 and in children 2 years and older earlier this year. The current approval converts these accelerated approvals to full approvals.
The conversion to a full approval is based on results from LIBRETTO-001 and LIBRETTO-121.
LIBRETTO-001 is a multicenter, open-label, multicohort phase I/II clinical trial that enrolled 65 patients with RET fusion-positive thyroid cancers that did not respond to prior radioactive iodine (if eligible). In this trial, responses to selpercatinib were observed in 85% of the 41 patients who had received prior systemic therapy other than radioactive iodine and in 96% of the 24 patients who had not received other systemic therapies. Responses persisted for a median of 26.7 months in previously treated patients; the median duration of response was not evaluable for patients who had not received prior systemic therapy.
LIBRETTO-121 is an international, single-arm, multicohort phase I/II clinical trial that enrolled 10 pediatric and young adult patients with advanced RET fusion-positive thyroid cancers that did not respond to available therapies. In this trial, 60% of patients experienced a response to selpercatinib, and 83% of these responses endured for at least 12 months.
For patients under 12 years of age, the recommended selpercatinib dose is based on body surface area and ranges from 40 mg three times daily to 160 mg twice daily. For patients 12 years of age and older, the recommended dose is 120 mg twice daily for patients who weigh less than 50 kg and 160 mg twice daily for those who weigh 50 kg or more.
Thyroid cancer arises in the thyroid, a gland found at the base of the throat that produces hormones. According to federal statistics, it was estimated that 44,020 individuals would be diagnosed with thyroid cancer and 2,170 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on June 12, 2024.