New Pediatric Indications for Selpercatinib 

The FDA approved the RET inhibitor selpercatinib for children with thyroid cancer and other solid tumors harboring various RET alterations. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to selpercatinib (Retevmo) for three new indications. The accelerated approval covers pediatric patients aged 2 years or older with: 

  • advanced or metastatic medullary thyroid cancer that requires systemic therapy and harbors a RET mutation; 
  • advanced or metastatic thyroid cancer that requires systemic therapy, harbors a RET gene fusion, and is refractory to radioactive iodine, if applicable; and 
  • locally advanced or metastatic solid tumors with a RET gene fusion that have progressed during or after treatment with a systemic therapy or have no alternative treatment options. 

Selpercatinib is a targeted therapy that inhibits mutant forms of the RET tyrosine kinase, a protein that is commonly mutated in several cancer types and can cause tumors to grow faster. Selpercatinib previously received accelerated approval for the same thyroid cancer indications in patients 12 and older in 2020 and for the same solid tumor indication in adults in 2022. 

Mutant forms of the RET protein kinase, shown here, can be targeted by selpercatinib, recently approved for certain pediatric cancers.

The current approval was based on results from the international, single-arm, multi-cohort, phase I/II LIBRETTO-121 clinical trial that included 25 patients aged 2 to 20 years with solid tumors harboring RET alterations that had no curative therapy options or were unresponsive to available therapies. Patients were treated until disease progression, unacceptable toxicity, or withdrawal from the trial. 

The overall response rate was 48% in the overall trial population, 43% among patients with RET-mutated medullary thyroid cancer, and 60% among patients with RET fusion-positive thyroid cancer. The median duration of response was not reached, and 92% of responses were ongoing after 12 months. 

For patients aged 2 to 12 years, the recommended dose of selpercatinib 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 if the patient weighs less than 50 kg and 160 mg twice daily if the patient weighs more than 50 kg. 

Thyroid cancer is a highly treatable disease that can occur in children and adults. According to federal statistics, it was estimated that 44,020 individuals in the United States would be diagnosed with thyroid cancer and 2,170 patients would die of the disease in 2024. 

An estimated 40% to 70% of sporadic (not inherited) medullary thyroid cancers harbor RET mutations. The prevalence of RET fusions ranges from 1% of anaplastic thyroid cancers to 10% to 30% of papillary thyroid cancers. RET fusions are also found in many other solid tumor types at varying frequencies. 

The FDA rendered its decision on May 29, 2024.