Anaplastic thyroid cancer (ATC) accounts for a small percentage of thyroid cancers. This type of thyroid cancer has a poor prognosis with nearly all cases being fatal. It is not responsive to typical thyroid cancer treatment like radioactive iodine. To extend life, usually a combination of treatments are needed including surgical resection, radiation therapy, targeted therapy, immunotherapy, and cytotoxic chemotherapy.
In today's side-by-side comparison, we look at the latest clinical practice guidelines from the American Thyroid Association (ATA), the National Comprehensive Cancer Network (NCCN), and the American Society of Clinical Oncology (ASCO) on systemic therapies for anaplastic thyroid cancer.
Guidelines for Comparison
| Item | 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer: American Thyroid Association Anaplastic Thyroid Cancer Guidelines Task Force | NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma Version 1.2025-March 25, 2025 | Systemic Treatment of Thyroid Cancer: ASCO Guideline |
|---|---|---|---|
| Authoring Organization | American Thyroid Association (ATA) | National Comprehensive Cancer Network (NCCN) | American Society of Clinical Oncology (ASCO) |
| Publication Date | March 2021 | March 2025 | April 2026 |
| Graded Recommendations | Yes | Yes | Yes |
| Uses Grade? | Yes | No, uses NCCN categories of evidence and consensus. | Yes |
| Links | Summary / Full Text | Full Text | Summary / Full Text |
Key Takeaways
One of the key differences in these guidelines is that both the ATA and NCCN break down their systemic therapy recommendations by cancer stage while ASCO makes generalized recommendations for patients with ATC.
BRAF/MEK Inhibitors:
- Recommendations for the use of BRAF/MEK inhibitors are for patients with BRAF V600E mutated ATC.
- All three guidelines make recommendations for dabrafenib plus trametinib.
- ASCO broadly recommends offering dabrafenib plus trametinib to patients with BRAF V600E mutated ATC.
- The ATA and NCCN both recommend dabrafenib plus trametinib for patients with stage IVc ATC.
- The ATA also recommends dabrafenib plus trametinib for patients with unresectable stage IVb ATC who decline radiotherapy.
- The ATA suggests offering dabrafenib plus trametinib as an option to patients with unresectable stage IVb ATC. Whereas the NCCN suggests offering this option to patients with borderline resectable stage IVa or IVb ATC.
- ASCO is the only guideline that suggests offering patients with BRAF V600E mutated ATC a PD1 inhibitor- pembrolizumab in addition to dabrafenib plus trametinib.
NTRK/RET Inhibitors:
- Recommendations for the use of NTRK inhibitors and RET inhibitors are for patients with ATC tumors harbouring NTRK or RET fusions.
- All three guidelines make recommendations for NTRK inhibitors-entrectinib and larotrectinib and RET inhibitor-selpercatinib.
- Both the ATA and NCCN also have recommendations for RET inhibitor-pralesetinib.
- The NCCN includes one additional NTRK inhibitor in their recommendations-repotrectinib.
- ASCO suggests NTRK or RET inhibitors be offered to patients with ATC.
- ATA suggests NTRK or RET inhibitors for patients with stage IVc ATC.
- NCCN recommends NTRK or RET inhibitors for stage IVc ATC and suggests they be offered as an option to patients with borderline resectable stage IVa or IVb ATC.
Multikinase Inhibitor (MKI)/Immune Checkpoint Inhibitors:
- Both the NCCN and ASCO make recommendations for the use of lenvatinib, pembrolizumab, and nivolumab.
- Additionally, ASCO makes a recommendation for ipilimumab.
- The ATA does not recommend a specific drug name, instead suggesting that programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PD-L1) inhibitors be considered in patients without other actionable targets who have high PD-L1 expression.
- The NCCN suggests MKI/immune checkpoint inhibitors for certain patients with stage IVc ATC.
- ASCO considers the use of MKI/immune checkpoint inhibitors for patients without genetic mutations or for those with disease progression following genomically targeted therapy.
Cytotoxic Chemotherapy:
- The ATA and NCCN both make recommendations for specific cytotoxic chemotherapy agents: paclitaxel, docatexel, doxorubicin, cisplatin, and carboplatin.
- The ATA recommends initiating chemotherapy early before mutational results become available.
- ASCO on the other hand recommends against offering chemotherapy to patients with genomic targets. Instead they suggest offering chemotherapy to those with disease progression following treatment with targeted therapy, MKIs, and immunotherapy.
- ATA and NCCN consider the use of chemotherapy for patients with stage IVc ATC and as adjuvant radiosensitizing therapy.
Comparison of Targeted / Systemic Therapies
| Genomic Target | Targeted / Systemic Therapy | ATA | NCCN | ASCO |
|---|---|---|---|---|
| BRAF V600E Mutation | Dabrafenib plus Trametinib | Recommended for stage IVc and unresectable IVb. Option for unresectable stage IVb. | Recommended for stage IVc. Option for borderline resectable stage IVa or IVb. | Recommended. |
| BRAF V600E Mutation | Dabrafenib plus Trametinib plus Pembrolizumab | Not addressed. | Not addressed. | Option. |
| NTRK or RET Fusions | Larotrectinib | Option for stage IVc. | Recommended for stage IVc. Option for borderline resectable stage Iva or IVb. | Option. |
| NTRK or RET Fusions | Entrectinib | Option for stage IVc. | Recommended for stage IVc. Option for borderline resectable stage Iva or IVb. | Option. |
| NTRK or RET Fusions | Repotrectinib | Not addressed. | Recommended for stage IVc. Option for borderline resectable stage Iva or IVb. | Not addressed. |
| NTRK or RET Fusions | Selpercatinib | Option for stage IVc. | Recommended for stage Ivc. Option for borderline resectable stage Iva or IVb. | Option. |
| NTRK or RET Fusions | Pralsetinib | Option for stage IVc. | Recommended for stage IVc. Option for borderline resectable stage Iva or IVb. | Not addressed. |
| Absence of Targetable Mutations | PD-LA, PD 1 inhibitors | Option. | Specific drugs addressed below. | Specific drugs addressed below. |
| Absence of Targetable Mutations | Nivolumab | Not addressed. | Option for certain patients. | Not addressed. |
| Absence of Targetable Mutations | Ipilimumab plus Nivolumab | Not addressed. | Not addressed. | Option. |
| Absence of Targetable Mutations | Pembrolizumab | Not addressed. | Option for certain patients. | Not addressed. |
| Absence of Targetable Mutations | Pembrolizumab plus Lenvatinib | Not addressed. | Option for certain patients. | Option. |
| Absence of Targetable Mutations | Levatinib | Not addressed. | Not addressed. | Option. |
Comparison of Recommendations
| Systemic Therapy | ATA | NCCN | ASCO |
|---|---|---|---|
| BRAF/MEK Inhibitors | In BRAFV600E-mutated unresectable stage IVB ATC in which radiation therapy is feasible, chemoradiotherapy or neoadjuvant dabrafenib/trametinib represents alternatives to initial therapy. In BRAFV600E-mutated IVC and in unresectable IVB ATC patients who decline radiation therapy, initiation of BRAF/MEK inhibitors (dabrafenib plus trametinib) is recommended over other systemic therapies if available. | For patients with BRAF V600E mutated, borderline resectable IVa or IVb anaplastic thyroid cancer dabrafenib plus trametinib are options. For patients with BRAF V600E mutated IVc anaplastic carcinoma the preferred regimen is dabrafenib plus trametinib. | 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 with BRAF V600E–mutated ATC in the subsequent-line setting, clinicians may offer pembrolizumab, in combination with dabrafenib + trametinib. |
| NTRK/REK Inhibitors | In NTRK or RET fusion ATC patients with stage IVC disease, we suggest initiation of a TRK inhibitor (either larotrectinib or entrectinib) or RET inhibitor (either selpercatinib or pralsetinib), preferably in a clinical trial, if available. | For patients with NTRK gene fusion-positive, borderline resectable IVa or IVb anaplastic thyroid cancer entrectinib, larotrectinib, or repotrectinib are options. For patients with RET gene fusion-positive, borderline resectable IVa or IVb anaplastic thyroid cancer pralsetinib or selpercatinib are options. For patients with NTRK gene fusion-positive IVc anaplastic thyroid cancer entrectinib, larotrectinib, or repotrectinib are preferred. For patients with RET gene fusion-positive IVc anaplastic thyroid cancer pralsetinib or selpercatinib are preferred. | 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). |
| Multikinase Inhibitor (MKI)/Immune Checkpoint Inhibitors | In IVC ATC patients with high PD-L1 expression, checkpoint (PD-L1, PD1) inhibitors can be considered first-line therapy in the absence of other targetable alterations or as later line therapy, preferably in the context of a clinical trial. | For certain patients with IVc anaplastic thyroid cancer lenvatinib plus pembrolizumab may be useful. For certain patients with IVc anaplastic thyroid cancer nivolumab, pembrolizumab, or pembrolizumab plus lenvatinib may be useful. | For patient populations with ATC without a genomic mutation in the first-line setting, clinicians may offer lenvatinib. Qualifying Statement: Pembrolizumab may be added to lenvatinib based on results from a prospective study. 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 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. Qualifying Statement: Pembrolizumab may be added to lenvatinib based on results from a prospective study. 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. |
| Cytotoxic Chemotherapy | Among ATC patients with unresectable or advanced disease wishing aggressive therapy, we suggest early initiation of cytotoxic chemotherapy as an initial and potentially bridging approach until mutational interrogation results and/or mutationally specified therapies might be available, and if appropriate. In metastatic ATC patients lacking other therapeutic options including clinical trials, we suggest cytotoxic chemotherapy including a taxane and/or an anthracycline or taxane with or without cis- or carbo-platin. The use of cytotoxic chemotherapy involving a taxane (paclitaxel or docetaxel), administered with or without anthracyclines (doxorubicin) or platin (cisplatin or carboplatin), is recommended in patients treated with definitive-intention radiation. | For patients with IVc anaplastic thyroid cancer the following regimens may be recommended: doxorubicin, paclitaxel, carboplatin plus paclitaxel, or docetaxel plus doxorubicin. For certain patients with IVc anaplastic thyroid cancer who have had disease progression following prior treatment, pemetrexed plus carboplatin may be useful. For certain patients with IVc anaplastic thyroid cancer cisplatin plus doxorubicin may be useful. For patients with anaplastic thyroid cancer recommended adjuvant/radiosensitizing chemotherapy regimens include: carboplatin plus paclitaxel, docetaxel, or paclitaxel. | 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. |
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