Recommended First Line Targeted Therapy for RET and NTRK Fusion Positive Thyroid Cancer

Lori Wirth, MD, reviews recent National Comprehensive Cancer Network guideline updates for patients with radioactive iodine refractory differentiated thyroid cancer. For patients harboring RET or NTRK gene fusions, gene-specific targeted therapy is now recommended in the first-line setting. RET fusion–positive disease can be treated with selective inhibitors such as selpercatinib or pralsetinib, while NTRK fusion–positive tumors respond to TRK inhibitors like larotrectinib. These agents demonstrate high response rates exceeding 90% in some studies, along with durable clinical benefit and favorable tolerability compared with multikinase inhibitors. Notably, oncogenic kinase fusions are more frequently observed in younger patients, reinforcing the importance of comprehensive molecular testing in this population. The shift toward first-line use of targeted therapies reflects their superior efficacy and safety profiles, establishing them as preferred options in biomarker-driven management of advanced thyroid cancer.

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