ASCO Thyroid Cancer Guideline Updates Synthesize Evidence-Based Systemic Therapy Recommendations

On April 1, 2026, the American Society of Clinical Oncology (ASCO) published new clinical practice guidelines with evidence-based recommendations for the use of systemic therapy across thyroid cancer subtypes.¹ Read on for a snapshot of the most pertinent updates.

What are the ASCO guidelines for well-differentiated thyroid cancer?

The guidelines emphasize that the primary treatment of well-differentiated thyroid cancer should consist of surgery with or without radioactive iodine therapy. However, the guidelines outline the following for the treatment of patients with radioactive iodine–refractory recurrent or metastatic disease following primary treatment:

Multikinase inhibitors:

• Patients in the first-line setting: Oncologists should offer lenvatinib (Lenvima) or sorafenib (Nexavar; with the qualifying statement that although both agents are FDA approved in the first-line setting, the field lacks direct comparative evidence between the 2, and therefore, lenvatinib should be considered the first choice based on best available efficacy data).
  • Strength of recommendation: Strong
• Patients in subsequent-line settings: Oncologists should offer cabozantinib (Cabometyx).
  • Strength of recommendation: Strong

Genomically targeted therapies:

• Patients with genomic alterations in the first-line setting: Oncologists may offer genomically targeted therapy.
  • Strength of recommendation: Strong
• Patients in the first-line setting with NTRK or RET fusion–positive tumors: Oncologists should offer genomically targeted therapy (NTRK fusion–positive, larotrectinib [Vitrakvi] or entrectinib [Rozlytrek]; RET fusion–positive, selpercatinib [Retevmo]).
  • Strength of recommendation: Strong
• Patients in the first-line setting with BRAF V600E–mutated disease: Oncologists may offer genomically targeted therapy (trametinib [Mekinist] or dabrafenib [Tafinlar]).
  • Strength of recommendation: Conditional
• Patients in subsequent-line settings with genomic alterations who have previously received multikinase inhibitors: Oncologists should offer genomically targeted therapy (NTRK, BRAF V600E, or RET inhibitors).
  • Strength of recommendation: Strong

Immunotherapy:

• Patients in the first-line setting: Oncologists should not offer immunotherapy except in a clinical trial.
  • Strength of recommendation: Strong
• Patients in subsequent-line settings: Oncologists may add pembrolizumab (Keytruda) to lenvatinib following progression on lenvatinib monotherapy.
  • Strength of recommendation: Conditional

Cytotoxic chemotherapy:

• Patients in the first-line setting: Oncologists should not offer chemotherapy except in a clinical trial.
  • Strength of recommendation: Strong
• Patients in subsequent-line settings whose disease has progressed on genomically targeted therapies and multikinase inhibitors: Oncologists may offer cytotoxic chemotherapy.
  • Strength of recommendation: Conditional

What are the ASCO guidelines for differentiated high-grade or poorly differentiated thyroid cancer?

The guidelines emphasize that the primary treatment of differentiated high-grade or poorly differentiated thyroid cancer should consist of surgery with or without radioactive iodine therapy. However, the guidelines recommend the following for the treatment of patients with recurrent or metastatic disease following primary treatment:

Multikinase inhibitors:

• Patients in the first-line setting: Oncologists may offer lenvatinib or sorafenib (with the qualifying statement that although both agents are FDA approved in the first-line setting, the field lacks direct comparative evidence between the 2, and therefore, lenvatinib should be considered the first choice based on best available efficacy data).
  • Strength of recommendation: Conditional
• Patients in subsequent-line settings: There is insufficient evidence to recommend for or against the use of multikinase inhibitors.
  • Strength of recommendation: Conditional

Genomically targeted therapies:

• Patients with genomic alterations in the first- or subsequent-line settings with tumors harboring actionable genomic alterations: Oncologists may offer genomically targeted therapy (with the qualifying statement that there is insufficient clinical trial data to support the use of these agents in this setting to formally recommend for or against their routine use in this population).
  • Strength of recommendation: Conditional

Immunotherapy:

• Patients in the first- or subsequent-line settings: Oncologists may offer immunotherapy (with the qualifying statement that there is insufficient clinical trial data to support the use of these agents in this setting to formally recommend for or against their routine use in this population).
  • Strength of recommendation: Conditional

Cytotoxic chemotherapy:

• Patients in the first- or subsequent-line settings: There is insufficient evidence to recommend for or against the use of cytotoxic chemotherapy.
  • Strength of recommendation: Conditional

What are the ASCO guidelines for anaplastic thyroid cancer?

The guidelines emphasize multidisciplinary approaches that include surgery, systemic therapy, radiation, and airway management for anaplastic thyroid cancer. However, the following recommendations regard the use of systemic therapy at initial diagnosis and following primary therapies.

Multikinase inhibitors:

• Patients in the first-line setting without a genomic mutation: Oncologists may offer lenvatinib (with the qualifying statement that pembrolizumab may be added to lenvatinib).
  • Strength of recommendation: Conditional
• Patients in the subsequent-line setting without a genomic alteration whose disease progresses on lenvatinib with or without pembrolizumab: there is insufficient evidence in favor of using other agents; therefore, oncologists should suggest participation in a clinical trial.
  • Strength of recommendation: Conditional

Genomically targeted therapies:

• Patients in the first-line setting with BRAF V600E–mutated disease: oncologists should offer BRAF- or MEK-directed therapy (trametinib or dabrafenib).
  • Strength of recommendation: Strong
  • Oncologists may also offer BRAF- or MEK-directed therapy (trametinib or dabrafenib) in combination with pembrolizumab.
    • Strength of recommendation: Conditional
• Patients in the first-line setting with NTRK or RET fusion–positive tumors: oncologists may offer NTRK- or RET-targeted therapy (NTRK fusion–positive, larotrectinib or entrectinib; RET fusion–positive, selpercatinib).
  • Strength of recommendation: Conditional
• Patients in the subsequent-line setting with disease progression on genomically targeted therapy: oncologists may suggest clinical trial participation; if clinical trials are not available, lenvatinib may be offered (with the qualifying statement that pembrolizumab may be added to lenvatinib).
  • Strength of recommendation: Conditional

Immunotherapy:

• Patients in the first-line setting without a genomic mutation: oncologists may offer lenvatinib plus pembrolizumab or ipilimumab (Yervoy) plus nivolumab (Opdivo).
  • Strength of recommendation: Conditional
• Patients in subsequent-line settings with BRAF V600E–mutated disease: oncologists may offer pembrolizumab in combination with dabrafenib and trametinib.
  • Strength of recommendation: Conditional

Cytotoxic chemotherapy:

• Patients in the first-line setting who are candidates for genomically targeted therapies or multikinase inhibitors: Oncologists should not offer cytotoxic chemotherapy beyond the context of a clinical trial.
  • Strength of recommendation: Strong
• Patients in subsequent-line settings whose disease has progressed on genomically targeted therapies, multikinase inhibitors, and immunotherapy: Oncologists may offer cytotoxic chemotherapy.
  • Strength of recommendation: Conditional

What are the ASCO guidelines for medullary thyroid cancer?

The guidelines emphasize that the primary treatment for medullary thyroid cancer is surgery. However, the guidelines outline the following for the treatment of patients with recurrent or metastatic disease following primary treatment:

Multikinase inhibitors:

• Patients in the first-line setting with RET wild-type disease: Oncologists should offer vandetanib (Caprelsa) or cabozantinib.
  • Strength of recommendation: Strong
• Patients in subsequent-line settings with RET wild-type disease whose disease has progressed on vandetanib or cabozantinib: Oncologists should recommend participation in clinical trials. If no clinical trials are available, oncologists may offer vandetanib to patients who have progressed on cabozantinib or vice versa.
  • Strength of recommendation: Conditional

Genomically targeted therapies:

• Patients in the first-line setting with RET-mutant disease: Oncologists should offer selpercatinib.
  • Strength of recommendation: Strong
• Patients in subsequent-line settings with RET-mutant disease whose disease has progressed on selpercatinib: Oncologists should recommend participation in clinical trials. If no clinical trials are available, oncologists may offer cabozantinib or vandetanib.
  • Strength of recommendation: Conditional

Immunotherapy:

• Patients in the first- and subsequent-line settings: Oncologists should not offer immunotherapy except in a clinical trial.
  • Strength of recommendation: Strong

Cytotoxic chemotherapy:

• Patients in the first-line setting: Oncologists should not offer cytotoxic chemotherapy outside the context of a clinical trial.
  • Strength of recommendation: Strong
• Patients in subsequent-line settings whose disease has progressed on genomically targeted therapies and multikinase inhibitors: Oncologists may offer cytotoxic chemotherapy.
  • Strength of recommendation: Conditional

How can oncology teams and patients effectively communicate with each other for shared decision-making during thyroid cancer treatment?

The guidelines also include a section with recommendations for educational, empowering communication between oncology teams and patients regarding patient goals, educational resources, support services, and treatment expectations, as well as for engaging follow-up plans. The guidelines include sample questions that patients can discuss with their care teams, which are based on insights from the updated ASCO Patient-Clinician Communication Guidelines, published in March 2026.²

References

1. Saba NF, Ismaila N, Adkins D, et al. Systemic treatment of thyroid cancer: ASCO Guideline. J Clin Oncol. Published online April 1, 2026. doi:10.1200/JCO-26-00235
2. Gilligan T, Bohlke K, Alpert AB, et al. Patient-clinician communication: ASCO Guideline Update. J Clin Oncol. 2026;44(11):1040-1057. doi:10.1200/JCO-26-00118