Selpercatinib (Retevmo) in Thyroid Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Selpercatinib (Retevmo):
    • Is a highly selective RET kinase inhibitor:
      • Designed to block aberrant RET signaling in cancers with RET mutations or fusions
  • It’s FDA-approved for:
    • Adult and pediatric patients (≥ 2 years):
      • With advanced / metastatic RET fusion–positive thyroid cancer that is radioactive iodine (RAI)-refractory and requires systemic therapy
    • Also approved for RET-mutant medullary thyroid cancer and RET fusion–positive non–small cell lung cancer
    • Clinical Evidence:
      • LIBRETTO‑001 Trial (RET Fusion –Positive Thyroid Cancer Cohorts):
        • Participants:
          • 65 adult patients with RET fusion + DTC, including both RAI – refractory and treatment – naïve individuals
        • Efficacy:
          • Previously treated cohort (n=41): ORR 85% (95% CI: 71–94%), median duration of response (DOR) 26.7 months
          • Treatment-naïve cohort (n=24): ORR 96%, median DOR not yet reached (≥ 42.8 months)
        • Progression-free survival for RET fusion – positive thyroid cancers:
          • Estimated around 22 months, consistent with real-world data
  • Safety Profile:
    • Common side effects include:
      • Hypertension
      • Dry mouth
      • Diarrhea
      • Fatigue
      • Edema
      • Rash
      • Laboratory abnormalities like elevated ALT / AST 
    • Most AEs were grade 1 to 2, with manageable toxicity:
      • Low discontinuation rates (~ 2%)
  • Emerging Roles:
    • Neoadjuvant Use and Radioactive Iodine Re-sensitization:
      • Active clinical trials (e.g., NCT04759911, NCT06458036) are evaluating selpercatinib as neoadjuvant therapy prior to surgery or RAI in RET fusion–positive DTC, with the goal to shrink tumors and enhance iodine uptake
  • Clinical Implications:
    • First-line option for advanced / metastatic RET fusion + DTC, especially when RAI has failed or is inapplicable
    • Offers exceptional response rates and durable remissions
    • Potential for earlier use, including neoadjuvant settings or combination with RAI, pending trial results
    • Recommended tumor genomic profiling for all advanced thyroid cancers to identify RET alterations and enable targeted therapy
  • Future Outlook:
    • Neoadjuvant and combinatorial strategies may broaden selpercatinib’s role in DTC
    • Ongoing trials will clarify its utility in enhancing RAI responsiveness and enabling less extensive surgery
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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