Dr Wirth on Questions About Selpercatinib Use in Advanced 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 remaining questions regarding the treatment of adult and pediatric patients at least 2 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory following the June 2024 FDA full approval of selpercatinib (Retevmo).

The FDA’s full approval of selpercatinib for this indication underscores the drug’s position as first-line treatment for RET-driven thyroid cancers, whether they are RET-mutated medullary thyroid cancers or RET fusion–positive follicular cell–derived thyroid cancers, for which radioactive iodine is not suitable, Wirth begins. Selpercatinib is already recognized as a category 1 agent in the National Comprehensive Cancer Network guidelines for this indication, according to Wirth. The full FDA approval reinforces the drug’s priority status, she explains. Furthermore, with robust safety and efficacy data now available for pediatric patients, selpercatinib is also established as the primary treatment choice for children with RET-driven thyroid cancers, Wirth states.

One significant, yet unresolved, question in the field concerns the timing of initiating selpercatinib therapy, she continues. Historically, because some thyroid cancers can be indolent and asymptomatic for extended periods, and older treatments, such as multikinase inhibitors, were associated with significant adverse effects (AEs), clinicians often delayed therapy to balance efficacy with quality of life (QOL), Wirth emphasizes. The question now is whether it remains appropriate to delay treatment in patients with RET-driven thyroid cancers, or whether starting selpercatinib earlier in the disease course would provide better outcomes, Wirth adds.

Determining treatment timing is crucial because early intervention might improve long-term efficacy, but the optimal timing for initiating selpercatinib treatment in asymptomatic or slowly progressing cases remains uncertain, she expands. Thus, determining the best approach for timing therapy with selpercatinib is an important consideration for clinicians treating patients with RET-driven thyroid cancers, Wirth emphasizes. The balance between managing potential progression and maintaining QOL without unnecessary delays in effective treatment is at the forefront of ongoing discussions and research in the field, Wirth concludes.