PD-1 Blockade in Anaplastic Thyroid Carcinoma

Journal of Clinical Oncology, vol. 38, pp. 2620–2627

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.

Authors 22

1. Jaume Capdevila

   Universitat Autònoma de Barcelona · Vall d'Hebron Hospital Universitari · Vall d'Hebron Institute of Oncology

   Affiliation as printed

   Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain

2. Lori J. Wirth

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Massachusetts General Hospital and Harvard Medical School, Boston, MA

   Massachusetts General Hospital and Harvard Medical School , Boston, MA ,

3. Thomas Ernst

   Jena University Hospital

   Affiliation as printed

   Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

4. Santiago Ponce-Aix

   Hospital Universitario 12 De Octubre

   Affiliation as printed

   University Hospital 12 de Octubre, Madrid, Spain

5. Chia‐Chi Lin

   National Taiwan University Hospital

   Affiliation as printed

   National Taiwan University Hospital, Taipei, Taiwan

   National Taiwan University Hospital, Taipei, Taiwan#TAB#

6. Rodryg Ramlau

   Poznan University of Medical Sciences

   Affiliation as printed

   Poznań University of Medical Sciences, Poznań, Poland

   Poznan University of medical Sciences, Poznan, Poland

7. Marcus Otho Butler

   University Health Network · Princess Margaret Cancer Centre

   Affiliation as printed

   Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada

   Princess Margaret Cancer Centre, University Health Network , Toronto, Ontario, Canada

8. Jean‐Pierre Delord

   Institut universitaire du cancer de Toulouse Oncopole

   Affiliation as printed

   IUCT Oncopole, Toulouse, France

9. Hans A. J. Gelderblom Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center, Leiden, the Netherlands

10. Paolo A. Ascierto

    Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

    Affiliation as printed

    Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy

11. Angelica Fasolo

    IRCCS Ospedale San Raffaele

    Affiliation as printed

    San Raffaele Hospital, Milan, Italy

12. Dagmar Führer

    Essen University Hospital

    Affiliation as printed

    University Hospital Essen, Essen, Germany

13. Marie Luise Hütter‐Krönke

    University Hospital Ulm

    Affiliation as printed

    University Hospital Ulm, Ulm, Germany

14. Patrick M. Forde

    Johns Hopkins University · Johns Hopkins Medicine · Sidney Kimmel Comprehensive Cancer Center

    Affiliation as printed

    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD

15. Anna Wrona

    University Clinical Centre

    Affiliation as printed

    Uniwersyteckie Centrum Kliniczne, Gdansk, Poland

16. Armando Santoro

    Humanitas University · IRCCS Humanitas Research Hospital

    Affiliation as printed

    IRCCS Humanitas Clinical and Research Center–Humanitas University, Rozzano, Italy

17. Peter M. Sadow

    Harvard University · Massachusetts General Hospital

    Affiliation as printed

    Massachusetts General Hospital and Harvard Medical School, Boston, MA

    Massachusetts General Hospital and Harvard Medical School , Boston, MA ,

18. Sebastian Szpakowski
    Affiliation as printed

    Novartis Institutes for BioMedical Research, Cambridge, MA

19. Hongqian Wu
    Affiliation as printed

    Novartis Pharmaceuticals, East Hanover, NJ

20. Geraldine Bostel

    Novartis Institutes for BioMedical Research

    Affiliation as printed

    Novartis Institutes for BioMedical Research, Basel, Switzerland

21. Jason Edward Faris
    Affiliation as printed

    Novartis Institutes for BioMedical Research, Cambridge, MA

22. Matthew Hiram Taylor

    Oregon Health & Science University

    Affiliation as printed

    Oregon Health & Science University, Portland, OR