The American Society of Clinical Oncology (ASCO) recently released the clinical practice guideline Systemic Treatment of Thyroid Cancer. Included within the guideline are 32 recommendations grouped by thyroid cancer type and an associated clinical question. 

The ASCO systemic therapy for thyroid cancer recommendations address and are grouped by four different types of thyroid cancer: well-differentiated, differentiated high-grade or poorly differentiated, anaplastic, and medullary. Today, we’re taking a look at the four groups of recommendations, included in the 2026 Systemic Treatment of Thyroid Cancer guideline. View the full-text version of the guideline to view the clinical questions associated with each grouping of recommendations, along with the most thorough look at each individual recommendation. 

Recommendations from the 2026 Update:

Well-Differentiated (papillary, follicular, oncocytic)

  • For patient populations in the first-line setting, clinicians should offer lenvatinib or sorafenib.
  • For patient populations in the subsequent line setting, clinicians should offer cabozantinib.
  • For patient populations with genomic alterations in the first-line setting, clinicians may offer genomically targeted therapy.
  • For patient populations in the first-line setting, whose tumor harbors NTRK or RET fusions, clinicians should offer genomically targeted therapies (larotrectinib or entrectinib for NTRK, selpercatinib for RET) prior to treatment with MKIs.
  • For patient populations in the first-line setting, whose tumor harbors a BRAF V600E mutation, clinicians may offer genomically targeted therapies (dabrafenib or trametinib) prior to treatment with MKIs.
  • For patient populations with genomic alterations in the subsequent line setting, who have been previously treated with MKIs, clinicians should offer genomically targeted therapies (NTRK, BRAF V600E, or RET inhibitors).
  • For patient populations in the first-line setting, clinicians should not offer immunotherapy outside of a clinical trial.
  • For patient populations in the subsequent line setting, clinicians may add pembrolizumab to lenvatinib to patients who have disease progression on lenvatinib alone.
  • For patient populations in the first-line setting, clinicians should not offer cytotoxic chemotherapy outside of a clinical trial. 
  • For patient populations in the subsequent line setting, who have disease progression on genomically targeted therapies and MKIs, clinicians may offer treatment with cytotoxic chemotherapy.

Differentiated High-Grade (DHGTC) or Poorly Differentiated (PDTC)

  • For patient populations in the first-line setting, clinicians may offer lenvatinib or sorafenib.
  • For patient populations in the subsequent line setting, there is insufficient data to recommend for or against the use of MKIs.
  • For patient populations in the first or subsequent line settings, if their tumors harbor actionable genomic alterations, genomically targeted therapies may be offered.
  • For patient populations in the first or subsequent line settings, immunotherapy (such as programmed cell death protein 1 [PD-1] or programmed death ligand 1 [PD-L1] inhibitors) may be offered as a treatment option.
  • For patient populations in the first or subsequent line settings, there is insufficient data to recommend for or against the use of cytotoxic chemotherapy.

Anaplastic

  • For patient populations with anaplastic thyroid cancer (ATC) without a genomic mutation in the first-line setting, clinicians may offer lenvatinib.
  • For patient populations with ATC without a genomic mutation in the subsequent line setting, who have disease progression on lenvatinib or lenvatinib + pembrolizumab, participation in a clinical trial is recommended given the lack of evidence supporting the use of other agents.
  • For patient populations with BRAF V600E mutated ATC in the first line setting, clinicians should offer BRAF or MEK inhibitor targeted therapy (dabrafenib and trametinib).
  • For patient populations with BRAF V600E mutated ATC in the first line setting, clinicians may offer BRAF or MEK inhibitor targeted therapy (dabrafenib and trametinib) + pembrolizumab.
  • For patient populations in the first-line setting, whose tumor harbors NTRK or RET fusions, clinicians may offer NTRK or RET targeted therapy (larotrectinib or entrectinib for NTRK, selpercatinib for RET).
  • For patient populations in the subsequent line setting whose disease progressed on genomically targeted therapy, participation in clinical trials is recommended. If not available, lenvatinib may be offered.
  • For patient populations with ATC without a genomic mutation in the first-line setting, clinicians may offer lenvatinib + pembrolizumab or ipilimumab + nivolumab.
  • For patient populations with BRAF V600E mutated ATC in the subsequent line setting, clinicians may offer pembrolizumab, in combination with dabrafenib + trametinib. 
  • For patient populations in the first-line setting who are candidates for genomically targeted therapy or MKIs, clinicians should not offer cytotoxic chemotherapy outside of a clinical trial.
  • For patient populations in the subsequent line setting, who have disease progression on genomically targeted therapies, MKIs, and immunotherapy, clinicians may offer cytotoxic chemotherapy.

Medullary

  • For patient populations with RET wild-type disease in the first-line setting, clinicians should offer cabozantinib or vandetanib.
  • For patient populations with RET wild-type disease in the subsequent line setting, who have disease progression on cabozantinib or vandetanib, participation in clinical trials is recommended. If not available, patients with disease that progressed on cabozantinib may be offered vandetanib or vice versa.
  • For patient populations with RET mutant disease in the first line setting, clinicians should offer selpercatinib.
  • For patient populations with RET mutant disease in the subsequent line setting, who have disease progression on selpercatinib, participation in clinical trials is recommended. If not available, patients may be offered vandetanib or cabozantinib.
  • For patient populations in the first and subsequent line setting, clinicians should not offer immunotherapy outside of a clinical trial.
  • For patient populations in the first-line setting, clinicians should not offer cytotoxic chemotherapy outside of a clinical trial. 
  • For patient populations in the subsequent line setting, whose disease progressed on genomically targeted therapies and MKIs, clinicians may offer treatment with cytotoxic chemotherapy.

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