Improved Survival of Advanced-Stage Anaplastic Thyroid Cancer With Systemic Therapy

Laryngoscope. 2025 Jan;135(1):478-484. doi: 10.1002/lary.31712. Epub 2024 Aug 20.

Abstract

Objectives: Anaplastic thyroid cancer (ATC) is the most aggressive and fatal thyroid malignancy. Currently, there still exists a paucity of literature studying the relationship between available ATC-targeted therapy, immunotherapy, and survival. We aim to investigate how systemic therapies affect survival outcomes in ATC.

Methods: A single-tertiary-institution chart review of patients diagnosed with advanced-stage ATC, and who underwent surgery as part of their treatment, was performed between 2000 and 2023, with 41 patients included. Demographics, clinical characteristics, and survival data were collected and analyzed via Kaplan-Meier and Cox proportional hazards analyses.

Results: 54% of patients were female, and average age was 67.4 years old. The most common mutations identified were BRAF (15 patients), p53 (9 patients), and p63 (2 patients). A total of 18 patients utilized targeted or immunotherapy, with Trametinib and Dabrafenib (9 patients) as the most common agents used. Two-year overall survival was 24%, and 5-year overall survival was 23%, with median survival time of 7.6 months. Kaplan-Meier analysis demonstrated improved survival in patients who received chemotherapy (p = 0.048). Cox proportional hazards analysis demonstrated that patients treated with immunotherapy or targeted therapy had a statistically significant increase in survival compared with patients who did not receive these therapies (p = 0.016). Additionally, females and those with a p63 mutation demonstrated improved survival outcomes (p = 0.010, p = 0.001).

Conclusions: Targeted therapy and immunotherapy use should be strongly considered when treating patients with ATC. Further studies into novel drugs targeting immune checkpoints and combination therapy are needed to better optimize treatment of patients with ATC.

Level of evidence: 3 Laryngoscope, 135:478-484, 2025.

Keywords: ATC; anaplastic thyroid cancer; immunotherapy; systemic therapy; targeted therapy; thyroid.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Humans
  • Imidazoles / therapeutic use
  • Immunotherapy / methods
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Mutation
  • Neoplasm Staging
  • Oximes / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics
  • Pyridones / therapeutic use
  • Pyrimidinones / therapeutic use
  • Retrospective Studies
  • Survival Rate
  • Thyroid Carcinoma, Anaplastic* / drug therapy
  • Thyroid Carcinoma, Anaplastic* / genetics
  • Thyroid Carcinoma, Anaplastic* / mortality
  • Thyroid Carcinoma, Anaplastic* / pathology
  • Thyroid Carcinoma, Anaplastic* / therapy
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / mortality
  • Thyroid Neoplasms* / pathology
  • Thyroid Neoplasms* / therapy
  • Transcription Factors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins

Substances

  • Oximes
  • dabrafenib
  • trametinib
  • Pyridones
  • Imidazoles
  • Pyrimidinones
  • Proto-Oncogene Proteins B-raf
  • BRAF protein, human
  • TP63 protein, human
  • Tumor Suppressor Protein p53
  • Transcription Factors
  • Tumor Suppressor Proteins