PD-1 Blockade in Anaplastic Thyroid Carcinoma

Jaume Capdevila, Lori J. Wirth, Thomas Ernst, Santiago Ponce Aix, Chia Chi Lin, Rodryg Ramlau, Marcus O. Butler, Jean Pierre Delord, Hans Gelderblom, Paolo A. Ascierto, Angelica Fasolo, Dagmar Führer, Marie Luise Hütter-Krönke, Patrick M. Forde, Anna Wrona, Armando Santoro, Peter M. Sadow, Sebastian Szpakowski, Hongqian Wu, Geraldine BostelJason Faris, Scott Cameron, Andreea Varga, Matthew Taylor

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2620-2627
Number of pages8
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume38
Issue number23
DOIs
Publication statusPublished - Aug 10 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Capdevila, J., Wirth, L. J., Ernst, T., Ponce Aix, S., Lin, C. C., Ramlau, R., Butler, M. O., Delord, J. P., Gelderblom, H., Ascierto, P. A., Fasolo, A., Führer, D., Hütter-Krönke, M. L., Forde, P. M., Wrona, A., Santoro, A., Sadow, P. M., Szpakowski, S., Wu, H., ... Taylor, M. (2020). PD-1 Blockade in Anaplastic Thyroid Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 38(23), 2620-2627. https://doi.org/10.1200/JCO.19.02727