FDA Grants Traditional Approval to Selpercatinib for Advanced/Metastatic RET Fusion-Positive Thyroid Cancer

FDA Grants Traditional Approval to Selpercatinib for Advanced/Metastatic RET Fusion-Positive Thyroid Cancer

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 RET fusion-positive thyroid cancer who require systemic therapy and whose disease is refractory to radioactive iodine (if appropriate).

This traditional approval was based on findings from the LIBRETTO-001 trial (NCT03157128). This multicenter, open-label, multi-cohort trial included 65 patients with RET fusion-positive thyroid cancer whose disease was refractory to radioactive iodine (if it was an appropriate treatment option). Of note, patients naïve to systemic therapy and those previously treated were placed in separate cohorts.

The major efficacy outcome measures for the LIBRETTO-001 trial were overall response rate (ORR) and duration of response (DOR).

The ORR was 85% (95% CI, 71%-94%) in patients who were previously treated (n = 41) and 96% (95% CI, 79%-100%) in those who were systemic therapy naïve (n = 24). The median DOR was 26.7 months (95% CI, 12.1-not evaluable [NE]) and NE (95% CI, 42.8-NE), respectively.

Supportive evidence included selected data from the LIBRETTO-121 trial (J2G-OX-JZJJ; NCT03899792), particular ORR and DOR data from 10 pediatric and young adult patients with RET fusion-positive thyroid cancer. In this international, single-arm, multi-cohort trial, patients were also treated with selpercatinib. The ORR in this patient group was 60% (95% CI, 26%-88%), with 83% of patients experiencing a DOR of 12 months or longer, according to the FDA.

The most common adverse reactions, occurring in at least 25% of patients, included diarrhea, edema, dry mouth, fatigue, abdominal pain, hypertension, rash, constipation, headache, and nausea. In addition, the most common grade 3 or 4 laboratory abnormalities, occurring in at least 5% of patients, included decreased lymphocyte levels, increased aspartate aminotransferase levels, increased alanine aminotransferase levels, decreased calcium levels, and decreased sodium levels.

According to the FDA, the recommended dose for selpercatinib for pediatric patients between the ages of 2 years and 12 years is based on body surface area, whereas the dose for patients 12 years and older is based on weight.

Of note, selpercatinib received accelerated approval from the FDA in 2020 for this indication in patients aged 12 years and older.

Reference

FDA approves selpercatinib for RET fusion-positive thyroid cancer. News release. FDA. June 12, 2024. Accessed June 12, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-ret-fusion-positive-thyroid-cancer