Advanced Thyroid Carcinoma: Evolving Systemic Therapy Options

Presented by:
Lori J. Wirth
Search for other papers by Lori J. Wirth in
Current site
Google Scholar
PubMed Close
 MD
Volume/Issue:
Volume 19: Issue 5.5
Online Publication Date:
17 May 2021
DOI:
https://doi.org/10.6004/jnccn.2021.5018
Restricted access

Although multikinase inhibitors are established therapies in advanced thyroid cancers, treatment-related adverse events can lead to dose reductions and discontinuations, thereby limiting the effectiveness of these treatments. Gene‐specific treatments have emerged as new standard-of-care therapies, and continue to demonstrate efficacy and improved tolerability, although genotyping is needed to identify patients that would benefit from these therapies and more education is needed in regard to the optimal use of these novel agents. Additionally, the emergence of acquired resistance has become a new problem in the field.

Disclosures: Dr. Wirth has disclosed serving as a scientific advisor for Bayer HealthCare, Blueprint Medicines, Cue Biopharma, Eisai Inc., Eli Lilly and Company, Genentech, Inc., Loxo Oncology, Inc., and Merck & Co., Inc.

Correspondence: Lori J. Wirth, MD, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA 02114. Email: lwirth@mgh.harvard.edu
  • Collapse
  • Expand
Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
  • 1.

    Durante C , Haddy N , Baudin E , et al.. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 2006;91:2892–2899.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Barbet J , Campion L , Kraeber-Bodere F , et al.. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 2005;90:6077–6784.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Lin B , Ma H , Ma M , et al.. The incidence and survival analysis for anaplastic thyroid cancer: a SEER database analysis. Am J Transl Res 2019;11:5888–5896.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Brose MS , Nutting CM , Jarzab B , et al.. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet 2014 384:319–328.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Schlumberger M , Tahara M , Wirth LJ , et al.. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015;372:621–630.

  • 6.

    Wells SA , Robinson BG , Gagel RF , et al.. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012;30:134–141.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Elisei R , Schlumberger MJ , Muller SP , et al.. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 2013;31:3639–3646.

  • 8.

    Zehir A , Benayed R , Shah RH , et al.. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 2017;23:703–713.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Stransky N , Cerami E , Schalm S , et al.. The landscape of kinase fusions in cancer. Nat Commun 2014;5:4846.

  • 10.

    Shah MH , Wei L , Wirth LJ , et al.. Results of randomized phase II trial of dabrafenib versus dabrafenib plus trametinib in BRAF-mutated papillary thyroid carcinoma [abstract]. J Clin Oncol 2017;15(Suppl):Abstract 6022.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Subbiah V , Kreitman RJ , Wainberg ZA , et al.. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J Clin Oncol 2018;36:7–13.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Ciampi R , Romei C , Ramone T , et al.. Genetic landscape of somatic mutations in a large cohort of sporadic medullary thyroid carcinomas studied by next-generation targeted sequencing. iScience 2019;20:324–336.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Mulligan LM . RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer 2014;14:173–186.

  • 14.

    Wirth LJ , Sherman E , Robinson B , et al.. Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med 2020;383:825–835.

  • 15.

    Drilon A , Oxnard GR , Tan DSW , et al.. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 2020;383:813–824.

  • 16.

    Hu M , Subbiah V , Wirth LJ , et al.. Results from the registrational phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET mutation-positive medullary thyroid cancer (RET+ MTC) [abstract]. Ann Oncol 2020;31(Suppl 4):Abstract 19130.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Hong DS , DuBois SG , Kummar S , et al.. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol 2020;21:531–540.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Cabanillas ME , Drilon A, Farago AF , et al.. Larotrectinib treatment of advanced TRK fusion thyroid cancer [abstract]. Ann Oncol 2020;31(Suppl 4):Abstract 1916P.

  • 19.

    Solomon BJ , Tan L , Lin JJ , et al.. RET solvent front mutations mediate acquired resistance to selective RET inhibition in RET-driven malignancies. J Thorac Oncol 2020;15:541–549.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Lin JJ , Liu SV , McCoach CE , et al.. Mechanisms of resistance to selective RET tyrosine kinase inhibitors in RET fusion-positive non-small-cell lung cancer. Ann Oncol 2020;31:1725–1733.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    The Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell 2014;159:676–690.

  • 22.

    Yoo SK , Lee S, Kim SJ , et al.. Comprehensive analysis of the transcriptional and mutational landscape of follicular and papillary thyroid cancers. PLoS Genet 2016;12:e1006239.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Gopal RK , Kübler K , Calvo SE , et al.. Widespread chromosomal losses and mitochondrial DNA alterations as genetic drivers in Hürthle cell carcinoma. Cancer Cell 2018;34:242–255.e5.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Ganly I , Makarov V , Deraje S , et al.. Integrated genomic analysis of Hürthle cell cancer reveals oncogenic drivers, recurrent mitochondrial mutations, and unique chromosomal landscapes. Cancer Cell 2018;34:256–270.e5.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Landa I , Ibrahimpasic T , Boucai L , et al.. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 2016;126:1052–1066.

    • PubMed
    • Search Google Scholar
    • Export Citation
Copyright:
Copyright © 2021 by the National Comprehensive Cancer Network 2021
Page Numbers:
4
Article Category:
Research Article
Print Publication Date:
01 May 2021
Online Publication Date:
17 May 2021

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1798 761 111
PDF Downloads 637 58 5
EPUB Downloads 0 0 0