Selpercatinib Granted Traditional Approval for RET Fusion–Positive Thyroid Cancer

The FDA has granted traditional approval to selpercatinib (Retevmo®, Eli Lilly and Company) for adult and pediatric patients ≥2 years of age with advanced or metastatic rearranged during transfection (RET) fusion­­–positive thyroid cancer who require systemic therapy and are radioactive iodine (RAI)–refractory, if radioactive iodine is appropriate.

Selpercatinib was previously granted accelerated approval in 2020 for this indication for patients ≥12 years of age.

Why it matters: “RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers,” wrote Lori Wirth, MD, the Medical Director of the Center for Head and Neck Cancers at Massachusetts General Hospital, and colleagues, in their initial findings from the LIBRETTO-001 trial (NCT03157128). “In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.”

What they studied: Efficacy was assessed in the phase 1/2, open-label, multicohort, multicenter trial which studied 65 patients with RET fusion–positive thyroid cancer who were RAI-refractory, if RAI was an appropriate treatment option, and were systemic therapy–naive. Patients who were previously treated were put into separate cohorts.

The primary efficacy outcomes measured were overall response rate and duration of response.

What they found: In the 41 previously treated patients, selpercatinib produced an objective response rate of 85%, compared with the 24 systemic therapy–naive patients who achieved an objective response rate of 96%. In the previously treated population, the median duration of response was 26.7 months. Those who were systemic therapy–naive were not evaluable for duration of response.

Included in the objective response rate and duration of response data was supportive evidence from 10 pediatric and young adult patients with RET fusion–positive thyroid cancer treated in the LIBRETTO-121 study (NCT03899792). This was an international, single-arm trial studying selpercatinib in pediatric and young adult patients with advanced RET-altered solid tumors. The objective response rate in this population was 60%. As well, the observed duration of response was ≥12 months in 83% of patients.

Adverse events: The most common adverse events experienced in ≥25% of patients receiving selpercatinib were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities experienced by ≥5% of patients were decreased lymphocytes, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium.

Implementing into practice: “The implementation of effective molecular screening strategies for patients with either germline or somatic RET mutation in nonfamilial medullary thyroid cancer will be essential in identifying patients who may benefit from RET inhibition,” concluded Dr. Wirth.

Instructions: The recommended dosage of selpercatinib for pediatric patients two to <12 years of age is based on body surface area. For patients >12 years of age, dosage is based on weight. See the prescribing information for specific dosing information.

For More Information

Drilon A, Subbiah V, Gautschi O, et al (2023). Selpercatinib in patients with RET fusion-positive non-small-cell lung cancer: Updated safety and efficacy from the registrational LIBRETTO-001 phase I/II trial. J Clin Oncol, 41(2):385-394. DOI:10.1200/JCO.22.00393

Wirth LJ, Sherman E, Robinson B, et al (2020). Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med, 383(9):825-835. DOI:10.1056/NEJMoa2005651

Retevmo® (selpercatinib) prescribing information (2024). Eli Lilly and Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213246s008lbl.pdf

Clinicaltrials.gov (2024). A study of selpercatinib (LOXO-292) in participants with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001) (LIBRETTO-001). NLM identifier: NCT03157128.

US Food and Drug Administration (2024). FDA approves selpercatinib for RET fusion-positive thyroid cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-ret-fusion-positive-thyroid-cancer

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