FDA Approves Selpercatinib for RET+ Medullary Thyroid Cancer

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

The traditional approval was based on efficacy data from the randomized, multicenter, open-label, phase 3 LIBRETTO-531 trial (NCT04211337), designed to evaluate selpercatinib (160 mg twice daily) vs physician’s choice of cabozantinib (Cabometyx; 140 mg once daily) or vandetanib (Caprelsa; 300 mg once daily) in a 2:1 fashion among patients with advanced or metastatic RET-mutant medullary thyroid cancer.

Median progression-free survival (PFS), the trial’s primary end point, was not reached (NR; 95% CI, NE-NE) in the selpercatinib arm, compared with 16.8 months (95% CI, 12.2-25.1) in the physician’s choice arm, reducing the risk for disease worsening by 72% (HR, 0.28; 95% CI, 0.165-0.475; P < .0001).

The FDA approved selpercatinib for the treatment of patients with advanced or metastatic, RET-mutant medullary thyroid cancer.

“The clinical benefit of selpercatinib was supported by a pre-specified analysis of patient-reported comparative side effect impact; patients in the selpercatinib arm reported less time with severe side effect bother than those receiving cabozantinib or vandetanib,” the agency added in its release.

Lastly, the most common adverse events, occurring in 25% of patients treated with selpercatinib were hypertension, edema, dry mouth, fatigue, and diarrhea. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased alanine aminotransferase, decreased neutrophils, increased alkaline phosphatase, increased blood creatinine, decreased calcium, and increased aspartate aminotransferase.

“These data from the LIBRETTO-531 trial confirm the importance of selectively targeting RET-driven cancers and suggest [selpercatinib] should be considered the preferred first-line treatment for people with advanced RET-mutant medullary thyroid cancer,” David Hyman, MD, chief medical officer at Loxo Oncology at Eli Lilly and Company, stated in a press release announcing the trial’s topline data.2

The FDA noted that the recommended dose of selpercatinib for pediatric patients ranging in age from 2 to less than 12 years should be based on body surface area; however, for those aged 12 or older, the dose is based on weight.

The agent received accelerated approval for this indication for patients 12 years of age and older in 2020, followed by accelerated approval for this indication to pediatric patients 2 years of age and older on May 29, 2024.

Reference:

1. FDA News Release. FDA approves selpercatinib for RET fusion-positive medullary thyroid cancer. Published: September 27, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-ret-fusion-positive-medullary-thyroid-cancer?utm_medium=email&utm_source=govdelivery. Accessed: September 27, 2024.

2. Lilly’s Retevmo (selpercatinib) demonstrates superior progression-free survival compared to approved multikinase inhibitors in RET-mutant medullary thyroid cancer. News release. Eli Lilly and Company. August 22, 2023. Accessed August 22, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-retevmor-selpercatinib-demonstrates-superior-progression.