2. Academic Validation
  3. PD-1 Blockade in Anaplastic Thyroid Carcinoma

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

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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