FDA Approves Selpercatinib for Pediatric Patients With RET-Altered Metastatic Thyroid Cancer, Solid Tumors

FDA Approves Selpercatinib for Pediatric Patients With RET-Altered Metastatic Thyroid Cancer, Solid Tumors

The FDA granted accelerated approval to selpercatinib (Retevmo) for the treatment of pediatric patients aged 2 years and older with RET-altered metastatic thyroid cancer or solid tumors.¹

In particular, the approval was granted for the following pediatric patients aged 2 years and older:

• advanced or metastatic medullary thyroid cancer with a RET mutation requiring systemic therapy,
• advanced or metastatic thyroid cancer with a RET gene fusion requiring systemic therapy and are refractory to radioactive iodine if originally deemed appropriate, and
• locally advanced or metastatic solid tumors with a RET gene fusion that progressed on or after prior systemic treatment or those with no satisfactory alternative treatment options.

This marks the first FDA approval of a targeted therapy for pediatric patients younger than 12 years old with RET alterations, according to a release from the agency.

The FDA approval was based on findings from the LIBRETTO-121 (NCT03899792) trial, which evaluated the efficacy of selpercatinib in pediatric and young adult patients. In this international, single-arm, multi-cohort trial, patients received 92 mg/m2 of selpercatinib orally twice per day until unacceptable toxicity, disease progression, or another reason for treatment discontinuation. The primary efficacy population in this trial included 25 patients ages 2 years to 20 years with locally advanced or metastatic RET-activated solid tumors that were nonresponsive to available therapies or with no available standard systemic curative therapy.

The major efficacy outcome measures for the LIBRETTO-121 trial were confirmed overall response rate (ORR), as determined by blinded independent review committee, and duration of response (DOR).

The confirmed ORR per RECIST 1.1 was 48% (95% CI, 28%-69%), and the median DOR was not reached (95% CI, not evaluable [NE]-NE). At 12 months, 92% of patients who responded to selpercatinib remained in response. Durable responses to selpercatinib were observed in pediatric and young adult patients with RET fusion-positive thyroid cancer (n = 10; ORR = 60%; 95% CI, 26%-88%) and in those with RET-mutant medullary thyroid cancer (n = 14; ORR = 43%; 95% CI, 18%-71%).

The most common adverse reactions, occurring in at least 25% of patients, included diarrhea, musculoskeletal pain, nausea, headache, coronavirus infection, vomiting, fatigue, abdominal pain, hemorrhage, and pyrexia, according to the release. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 5% of patients, included decreased hemoglobin levels, decreased calcium levels, and decreased neutrophil levels.

The recommended dose of selpercatinib for pediatric patients ages 2 years to 12 years is based on surface area, according to the FDA.² The recommended dose for patients ages 2 years to 12 years who weigh less than 50 kg is 120 mg orally twice daily, which should be increased to 160 mg orally twice daily for those who weigh 50 kg or greater. For those ages 12 years and older, the dose is based on weight: 40 mg orally 3 times daily for a body surface area between 0.33 and 0.65 m²; 80 mg orally twice daily for 0.66 to 1.08 m²; 120 mg orally twice daily for 1.09 to 1.52 m²; and 160 mg orally twice daily for 1.53 m² and greater. It is noted to reduce the dose of selpercatinib in patients with severe hepatic impairment.

Selpercatinib is available in capsules (40 mg and 80 mg) and in tablets (40 mg, 80 mg, 120 mg, and 160 mg).

Although there are no contraindications for selpercatinib, there are several warnings and precautions noted in the prescribing information including hepatotoxicity, interstitial lung disease/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, risk of impaired wound healing, hypothyroidism, embryo-fetal toxicity, and slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients.

Of note, selpercatinib was previously granted an accelerated approval from the FDA for these thyroid cancer indications in adult and pediatric patients aged 12 years and older.¹ It also received an accelerated approval for the solid tumor indication in adult patients.

References

1. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. News release. FDA. May 29, 2024. Accessed May 29, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selpercatinib-pediatric-patients-two-years-and-older-ret-altered
2. Selpercatinib. Eli Lilly and Company. May 2024. Accessed May 29, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213246s012lbl.pdf