PD-1 Blockade in Anaplastic Thyroid Carcinoma

  • J Clin Oncol. 2020 Aug 10;38(23):2620-2627. doi: 10.1200/JCO.19.02727.
Jaume Capdevila  1 ,  Lori J Wirth  2 ,  Thomas Ernst  3 ,  Santiago Ponce Aix  4 ,  Chia-Chi Lin  5 ,  Rodryg Ramlau  6 ,  Marcus O Butler  7 ,  Jean-Pierre Delord  8 ,  Hans Gelderblom  9 ,  Paolo A Ascierto  10 ,  Angelica Fasolo  11 ,  Dagmar Führer   #  12 ,  Marie Luise Hütter-Krönke  13 ,  Patrick M Forde  14 ,  Anna Wrona  15 ,  Armando Santoro  16 ,  Peter M Sadow  2 ,  Sebastian Szpakowski  17 ,  Hongqian Wu  18 ,  Geraldine Bostel  19 ,  Jason Faris  17 ,  Scott Cameron  17 ,  Andreea Varga  20 ,  Matthew Taylor  21
Affiliations
  • 1. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 2. Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • 3. Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
  • 4. University Hospital 12 de Octubre, Madrid, Spain.
  • 5. National Taiwan University Hospital, Taipei, Taiwan.
  • 6. Poznań University of Medical Sciences, Poznań, Poland.
  • 7. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • 8. IUCT Oncopole, Toulouse, France.
  • 9. Leiden University Medical Center, Leiden, the Netherlands.
  • 10. Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
  • 11. San Raffaele Hospital, Milan, Italy.
  • 12. University Hospital Essen, Essen, Germany.
  • 13. University Hospital Ulm, Ulm, Germany.
  • 14. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
  • 15. Uniwersyteckie Centrum Kliniczne, Gdansk, Poland.
  • 16. IRCCS Humanitas Clinical and Research Center-Humanitas University, Rozzano, Italy.
  • 17. Novartis Institutes for BioMedical Research, Cambridge, MA.
  • 18. Novartis Pharmaceuticals, East Hanover, NJ.
  • 19. Novartis Institutes for BioMedical Research, Basel, Switzerland.
  • 20. Gustave Roussy Cancer Campus, Paris, France.
  • 21. Oregon Health & Science University, Portland, OR.
  • # Contributed equally.
PMID: 32364844 DOI: 10.1200/JCO.19.02727
Abstract

Purpose: Anaplastic thyroid carcinoma is an aggressive malignancy that is almost always fatal and lacks effective systemic treatment options for patients with BRAF-wild type disease. As part of a phase I/II study in patients with advanced/metastatic solid tumors, patients with anaplastic thyroid carcinoma were treated with spartalizumab, a humanized monoclonal antibody against the programmed death-1 (PD-1) receptor.

Methods: We enrolled patients with locally advanced and/or metastatic anaplastic thyroid carcinoma in a phase II cohort of the study. Patients received 400 mg spartalizumab intravenously, once every 4 weeks. The overall response rate was determined according to RECIST v1.1.

Results: Forty-two patients were enrolled. Adverse events were consistent with those previously observed with PD-1 blockade. Most common treatment-related adverse events were diarrhea (12%), pruritus (12%), fatigue (7%), and pyrexia (7%). The overall response rate was 19%, including three patients with a complete response and five with a partial response. Most patients had baseline tumor biopsies positive for PD-L1 expression (n = 28/40 evaluable), and response rates were higher in PD-L1-positive (8/28; 29%) versus PD-L1-negative (0/12; 0%) patients. The highest rate of response was observed in the subset of patients with PD-L1 ≥ 50% (6/17; 35%). Responses were seen in both BRAF-nonmutant and BRAF-mutant patients and were durable, with a 1-year survival of 52.1% in the PD-L1-positive population.

Conclusion: To our knowledge, this is the first clinical trial to show responsiveness of anaplastic thyroid carcinoma to PD-1 blockade.

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