Dr Wirth on the Safety of Selpercatinib in RET Fusion+ Thyroid Cancer

Lori Wirth, MD, associate professor, medicine, Harvard Medical School; medical director, Center for Head and Neck Cancers; Massachusetts General Hospital, discusses the safety of treatment with selpercatinib (Retevmo) in adult and pediatric patients at least 2 years of age with advanced or metastatic RET fusion–positive thyroid cancer.

In June 2024, the FDA granted full approval to selpercatinib for the treatment of patients in this population who require systemic therapy and are radioactive iodine (RAI) refractory, if RAI is appropriate. This full approval was supported by data from the phase 1/2 LIBRETTO-001 trial (NCT03157128), in which selpercatinib generated an overall response rate (ORR) of 85% (95% CI, 71%-94%) in previously treated patients (n = 41), and an ORR of 96% (95% CI, 79%-100) in patients who were naive to systemic therapy (n = 24). Notably, selpercatinib previously received accelerated approval from the FDA for the same indication in May 2020.

The safety profile of selpercatinib in the pediatric population was comparable to that of the adult population, Wirth begins. No dose-limiting toxicities (DLTs) were observed, and no patients discontinued the trial due to treatment-related adverse effects (AEs), she adds. Commontreatment-related AEs included diarrhea, fatigue, headache, and elevated aspartate transaminase and alanine transaminase, Wirth emphasizes.

Notably, patients with hereditary thyroid cancer frequently experience disease-related diarrhea at baseline, which can shift to constipation upon starting treatment with selpercatinib, she continues. This pattern was observed in the LIBRETTO-121 trial. Additionally, for healthcare providers treating young patients with these cancers, it is important to be aware that selpercatinib may affect the growth plate of long bones, Wirth states. This effect was observed in 1 pediatric patient enrolled onto the trial, she concludes.