Lenvatinib as Preferred First Line Therapy and Sequencing Strategies in RAI Refractory Thyroid Cancer

Lori Wirth, MD, outlines optimal first-line use and sequencing strategies for systemic therapy in radioactive iodine–refractory differentiated thyroid cancer. For patients without actionable RET or NTRK fusions, lenvatinib remains the preferred first-line option based on robust efficacy demonstrated in the SELECT trial, including a 65% response rate and median progression-free survival of approximately 18 months. Treatment initiation should be individualized, balancing disease burden, rate of progression, and quality-of-life considerations. Careful monitoring and proactive adverse event management—particularly hypertension and diarrhea—are critical to maintaining therapy. Subsequent treatment depends on molecular profile, with dabrafenib plus trametinib favored in BRAF V600E–mutant disease and cabozantinib in patients without this mutation. Emerging options, such as repotrectinib, address resistance in NTRK fusion–positive disease. These evolving strategies reflect increasingly personalized care pathways.

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