FDA Grants Traditional Approval to Selpercatinib in RET+ Medullary Cancer

Thyroid cancer, medical 3D illustration, front view: © Axel Kock - stock.adobe.com

The FDA granted traditional approval to selpercatinib (Retevmo) for the treatment of adult and pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer with a RET mutation, as detected by an FDA-approved test, who require systemic therapy.¹

Findings from the phase 3 LIBRETTO-531 trial (NCT04211337) support this regulatory decision as selpercatinib improved progression-free survival (PFS) vs physician's choice of cabozantinib (Cabometyx) or vandetanib (Caprelsa; HR, 0.280; 95% CI, 0.165-0.475; P <.0001) in this study. With selpercatinib, the median PFS was not reached (95% CI, not evaluable [NE]-NE) vs 16.8 months (95% CI,12.2-25.1) with cabozantinib or vandetanib. This translated to a 72% reduction in the risk of disease progression or death.

Looking at safety data, toxicities reported in 25% of patients or more consisted of hypertension, edema, dry mouth, fatigue, and diarrhea. Grade 3 or 4 laboratory abnormalities occurring in more than 5% of patients included decreased lymphocytes, increased alanine aminotransferase, decreased neutrophils, increased alkaline phosphatase, increased blood creatinine, decreased calcium, and increased aspartate aminotransferase.

About Phase 3 LIBRETTO-531 Trial

LIBRETTO-531 enrolled patients at least 12 years old with pathologically confirmed, unresectable, locally advanced or metastatic medullary thyroid cancer.² Patients were required to have had no prior exposure to kinase inhibitors, have radiologic progressive disease by RECIST 1.1 criteria, and have a prospectively identified pathogenic RET alteration. Enrollment was also open to those with an ECOG performance status of 0, 1, or 2, acceptable organ function, and those with normal electrolyte levels.

Once enrolled, patients were randomized in a 2:1 fashion and treated with 160 mg of selpercatinib twice a day, or physician's choice of cabozantinib once a day at a dose of 140 mg or vandetanib at 300 mg once daily. Treatment was given until progressive disease, intolerable toxicity, withdrawn consent, or death.

The primary end point was PFS by RECIST 1.1 criteria and blinded independent central review. Secondary end points of the trial were treatment failure-free survival by BICR and investigator, investigator-assessed PFS, overall survival by BICR and investigator assessment, and safety.

Previous FDA Approvals for Selpercatinib

In May 2020, the FDA granted accelerated approval to selpercatinib for adult and pediatric patients aged 12 years and older with advanced or metastatic RET-positive medullary thyroid cancer who require systemic treatment.³ The agent was then granted another accelerated approval in May 2024 for the treatment of pediatric patients aged 2 years and older with advanced or metastatic medullary thyroid cancer harboring a RET mutation who require systemic treatment, advanced or metastatic thyroid cancer harboring a RET gene fusion who need systemic therapy, and who are refractory to radioactive iodine, and select patients with locally advanced or metastatic solid tumors and a RET gene fusion.⁴

In June 2024, the FDA granted traditional approval to selpercatinib (Retevmo) for the treatment of adult and pediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine (RAI)-refractory.⁵

REFERENCES:

1. FDA approves selpercatinib for RET fusion-positive medullary thyroid cancer. FDA. September 27, 2024. Accessed September 27, 2024. https://tinyurl.com/y64scxxb

2. A study of oral LOXO-292 (selpercatinib) in pediatric participants with advanced solid or primary central nervous system (CNS) tumors (LIBRETTO-121). ClinicalTrials.gov. Updated March 7, 2024. Accessed September 27, 2024. https://clinicaltrials.gov/study/NCT03899792

3. FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. FDA. May 8, 2020. Accessed September 27, 2024. https://tinyurl.com/nhjk79xj

4. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. FDA. May 29, 2024. Accessed September 27, 2024. https://tinyurl.com/4jvrjuph

5. FDA approves selpercatinib for RET fusion-positive thyroid cancer. News release. FDA. June 12, 2024. Accessed September 27, 2024. https://tinyurl.com/3bar7hza