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PD-1 Blockade in Anaplastic Thyroid Carcinoma

Capdevila, Jaume, Wirth, Lori J, Ernst, Thomas, Ponce Aix, Santiago, Lin, Chia-Chi, Ramlau, Rodryg, Butler, Marcus O, Delord, Jean-Pierre, Fuhrer, Dagmar, Hutter-Kronke, Marie-Luise, Forde, Patrick M, Wrona, Anna, Santoro, Armando, Sadow, Peter M, Szpakowski, Sebastian, Wu, Hongqian, Bostel, Geraldine, Faris, Jason, Cameron, Scott, Varga, Andreea, Taylor, Matthew and Arkoski, Peter (2020) PD-1 Blockade in Anaplastic Thyroid Carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. pp. 1-9. ISSN 15277755


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.

Item Type: Article
Date Deposited: 09 Jun 2020 00:45
Last Modified: 09 Jun 2020 00:45


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