This week's episode walks through the new ASCO guideline on systemic therapy for thyroid cancer (Saba et al., JCO, April 2026) — 32 recommendations across well-differentiated, DHGTC/PDTC, anaplastic, and medullary disease, distilled from 66 studies.

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Systemic Treatment of Thyroid Cancer: the new ASCO guideline

• Test before you treat. In RAI-refractory differentiated disease, NTRK and RET fusions now move targeted agents (larotrectinib, entrectinib, selpercatinib) ahead of MKIs in the first line — a strong recommendation.
• Lenvatinib over sorafenib as the default first-line MKI in differentiated disease (SELECT: PFS 18.3 vs 3.6 mo, HR 0.21; ORR 65% vs 1.5%). Sorafenib is reasonable when uncontrolled hypertension or bleeding risk argues against lenvatinib.
• Cabozantinib is the second-line MKI after lenvatinib or sorafenib failure (COSMIC-311: PFS 11.0 vs 1.9 mo, HR 0.22).
• Medullary thyroid cancer splits on RET status. Selpercatinib is now first-line for RET-mutant MTC after LIBRETTO-531 (PFS not reached vs 16.8 mo, HR 0.28; HR for death 0.37). Cabozantinib or vandetanib remain first-line for RET wild-type.
• Anaplastic cancer is a multidisciplinary emergency. Determine BRAF V600E status fast — dabrafenib + trametinib (± pembrolizumab) can convert unresectable disease to operable. For non-mutated ATC, lenvatinib + pembrolizumab gave a median OS of 11.4 months in phase II.

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📄 Source paper: Saba NF, Ismaila N, Adkins D, et al. Systemic Treatment of Thyroid Cancer: ASCO Guideline. J Clin Oncol 2026. doi:10.1200/JCO-26-00235

Until next week, Head and Neck Oncology Journal Club Krishnakumar Thankappan