Real-World Experience with Targeted Therapy for the Treatment of Anaplastic Thyroid Carcinoma

Thyroid. 2018 Jan;28(1):79-87. doi: 10.1089/thy.2017.0285. Epub 2017 Dec 21.

Abstract

Background: Patients with anaplastic thyroid cancer (ATC) have a dismal prognosis, despite systemic cytotoxic chemotherapy. The objective of this study was to investigate the efficacy and safety of targeted therapy in ATC patients when used outside of a clinical trial.

Methods: This is a retrospective review from April 2015 to May 2016 at a single academic institution where 16 ATC patients receiving targeted therapy outside of a clinical trial were studied. Ten patients (eight BRAF wild type and two BRAFV600E mutant tumors) were started on lenvatinib, and six with BRAFV600E-mutated tumors received a combination of dabrafenib plus trametinib. Best response evaluated by RECIST v1.1, progression-free survival, and overall survival were determined. Adverse events were evaluated for safety.

Results: The majority of patients (63%) were men, and all had distant metastases or radiation-resistant primary disease at the time of treatment. In the entire cohort, 6/16 (38%) had a partial response, 6/16 (38%) had stable disease, and 2/16 (12%) had progressive disease. Two (12%) patients died before restaging. Median follow-up time was 11.8 months. Median progression-free survival was 3.7 months [confidence interval 1.8-7.6] in the entire cohort, 2.7 months for lenvatinib, and 5.2 months for dabrafenib plus trametinib. Median OS was 6.3 months [confidence interval 1.8-7.6] for the entire cohort, 3.9 months for lenvatinib, and 9.3 months for dabrafenib plus trametinib. Adverse events were as expected and manageable.

Conclusions: Targeted therapies, lenvatinib, and dabrafenib plus trametinib (for BRAFV600E mutants) may provide clinical benefit in ATC patients who are unable to participate in clinical trials, and toxicities are manageable.

Keywords: chemotherapy; dabrafenib; lenvatinib; thyroid cancer; trametinib; undifferentiated.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Male
  • Middle Aged
  • Mutation
  • Oximes / therapeutic use*
  • Phenylurea Compounds / therapeutic use*
  • Prognosis
  • Progression-Free Survival
  • Proto-Oncogene Proteins B-raf / genetics
  • Pyridones / therapeutic use*
  • Pyrimidinones / therapeutic use*
  • Quinolines / therapeutic use*
  • Retrospective Studies
  • Thyroid Carcinoma, Anaplastic / drug therapy*
  • Thyroid Carcinoma, Anaplastic / genetics
  • Thyroid Carcinoma, Anaplastic / pathology
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Treatment Outcome

Substances

  • Imidazoles
  • Oximes
  • Phenylurea Compounds
  • Pyridones
  • Pyrimidinones
  • Quinolines
  • trametinib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • lenvatinib
  • dabrafenib