Evolving Sequencing Strategies in Advanced Thyroid Cancer Based on Molecular Profile

Lori Wirth, MD, discusses how the expanding treatment landscape in advanced differentiated thyroid cancer has shifted focus toward optimal sequencing of therapies. For patients without actionable kinase fusions, lenvatinib remains the preferred first-line therapy. In the second-line setting, treatment selection is increasingly driven by tumor genomics. Patients with BRAF V600E–mutated disease benefit from dabrafenib plus trametinib based on phase 3 data, while those without this mutation derive benefit from cabozantinib, supported by results from the COSMIC-311 trial demonstrating improved progression-free survival. Data remain limited for sequencing after progression on RET or NTRK-targeted therapies; however, lenvatinib is a reasonable option in this context. Additionally, repotrectinib offers a targeted approach for patients with NTRK fusion–positive disease who develop resistance to first-generation TRK inhibitors, addressing kinase solvent front mutations.

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