According to a May 29th press release from the U.S. FDA, Retevmo (selpercatinib) from Eli Lilly is approved for the treatment of children aged 2 years and older with the following conditions:
• Advanced or metastatic medullary thyroid carcinoma requiring systemic therapy and having a RET mutation detected by an FDA-approved test;
• Advanced or metastatic thyroid cancer requiring systemic therapy and unresponsive to radioactive iodine (if appropriate) and having a RET gene fusion detected by an FDA-approved test;
• Locally advanced or metastatic solid tumors that have progressed during or after prior systemic therapy or for which there are no satisfactory alternative treatment options and have a RET gene fusion detected by an FDA-approved test.
Retevmo is a selective RET kinase inhibitor previously approved only for patients aged 12 years and older with RET-mutated medullary thyroid carcinoma and RET fusion-positive thyroid cancer, and adult patients with other RET fusion-positive solid tumors.
This marks the first time the FDA has approved a targeted therapy for children under 12 years of age with RET alterations.
This expanded approval is based on the open-label phase 1/2 LIBRETTO-121 trial (ClinicalTrials.gov identifier: NCT03899792), which evaluated selpercatinib in pediatric and young adult patients with advanced RET-activated solid tumors. Study participants received selpercatinib 92 mg/m² orally twice daily until disease progression, unacceptable toxicity, or other reasons for discontinuation. The primary efficacy population included 25 patients aged 2 to 20 years.
Results showed an overall response rate of 48% (95% CI, 28–69), as determined by a blinded independent review committee. The median duration of response was not reached (95% CI, non-evaluable [NE], NE); 92% of responders had a response lasting 12 months.
In 14 patients with RET-mutant medullary thyroid carcinoma, the established overall response rate was 43% (95% CI, 18-71), with 7% achieving complete response and 36% achieving partial response. The median duration of response was not reached (95% CI, NE, NE); 100% of responders had a response lasting at least 12 months, and 67% had a response lasting at least 18 months.
In 10 patients with RET fusion-positive thyroid carcinoma, the established overall response rate was 60% (95% CI, 26-88), with 30% achieving complete response and 30% achieving partial response. The median duration of response was not reached (95% CI, NE, NE); 83% of responders had a response lasting at least 12 months, and 50% had a response lasting at least 18 months.
The efficacy analysis also included one patient with treatment-unresponsive locally advanced refractory RET fusion-positive malignant schwannoma.
This trial included one adolescent who had experienced slipped femoral head/slipped upper femoral epiphysis (SCFE/SUFE). Pediatric patients receiving selpercatinib should be monitored for SCFE/SUFE symptoms and receive appropriate treatment.
The most common adverse reactions are musculoskeletal pain, diarrhea, headache, nausea, vomiting, COVID-19, abdominal pain, fatigue, fever, and bleeding. The most common grade 3 or 4 laboratory abnormalities are decreased calcium, hemoglobin, and neutropenia.
Currently, Retevmo is available in capsules at 40 mg and 80 mg dose strengths. New tablets at 40 mg, 80 mg, 120 mg, and 160 mg dose strengths have also been approved. The recommended dose for pediatric patients aged 2 to 12 years is based on body surface area.
