Selpercatinib Granted Accelerated Approval for Pediatric Patients With RET-Altered Metastatic Thyroid Cancer or Solid Tumors

The FDA has granted accelerated approval to selpercatinib (Retevmo®, Eli Lilly and Company) for pediatric patients two years of age and older with rearranged during transfection (RET) alterations, including:

  • Advanced/metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy
  • Advanced/metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and are radioactive iodine–refractory (if radioactive iodine is appropriate)
  • Locally advanced/metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or after prior systemic treatment or who have no other satisfactory treatment options

This marks the first FDA approval of a targeted therapy for pediatric patients under 12 years of age with RET alterations. Previously, selpercatinib was granted an accelerated approval for thyroid cancer indications in adults and pediatric patients 12 years of age and older, as well as for solid tumor indications in adults.

Why it matters: “Activating RET alterations are oncogenic drivers of select pediatric and adult cancers,” wrote Daniel Morgenstern, MD, an Oncologist and Assistant Professor at the Hospital for Sick Children in Toronto, Canada, and colleagues, in their published results of the LIBRETTO-121 trial (NCT03899792). “Selpercatinib is a first-in-class, highly selective and potent, central nervous system (CNS)–active RET kinase inhibitor. The manageable toxicity profile and durable antitumor activity in RET-altered cancers demonstrated in the LIBRETTO-001 phase 1/2 trial led to global approvals of selpercatinib in adults and adolescents with thyroid cancer and adults with non–small cell lung cancer (NSCLC).”

What they studied: Efficacy was measured in the phase 1/2, single-arm, multi-cohort, international trial, in which the primary efficacy population included 25 pediatric patients between the ages of two and 20 with locally advanced or metastatic RET-activated solid tumors non-responsive to available therapies or with no standard systemic curative therapy available. Patients received 92 mg/m2 of selpercatinib orally, twice daily, until disease progression or unacceptable toxicity.

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

What they found: As determined by Blinded Independent Review Committee (BICR), the confirmed overall response rate was 48%. The median duration of response was not reached. At the 12-month mark, 92% of patients who responded remained responsive. In addition, durable responses were observed in the pediatric and young adult patient population with RET-mutant MTC and RET fusion–positive thyroid cancer.

Adverse events: The most common adverse events experienced in ≥25% of patients receiving selpercatinib were musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage. The most common grade 3 or 4 laboratory abnormalities experienced by ≥5% of patients receiving selpercatinib were decreased calcium, decreased hemoglobin, and decreased neutrophils.

Conclusion: “These findings appear consistent with the adult trial results, showing preliminary evidence of safety and efficacy of selpercatinib in pediatric patients with RET-altered solid tumors,” concluded Dr. Morgenstern and colleagues in their publication of the preliminary results.

Instructions: The recommended dosage of selpercatinib for pediatric patients two to 12 years of age is based on body surface area and is based on weight for patients 12 years of age and older. Please refer to the prescribing information for specific dosing information.

For More Information

Morgenstern D, Mascarenhas L, Campbell M, et al (2021). Oral selpercatinib in pediatric patients (pts) with advanced RET-altered solid or primary CNS tumors: preliminary results from the phase 1/2 LIBRETTO-121 trial. J Clin Oncol (ASCO Annual Meeting Abstracts), 39(suppl_15). Abstract 10009. DOI:10.1200/JCO.2021.39.15_suppl.1000

Retevmo® (selpercatinib) prescribing information (2024). Eli Lilly and Company. Available at: (2024). A study of oral LOXO-292 (selpercatinib) in pediatric participants with advanced solid or primary central nervous system (CNS) tumors (LIBRETTO-121). NLM identifier: NCT03899792.

US Food and Drug Administration (2024). FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. Available at:

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