PD-1 Blockade in Anaplastic Thyroid Carcinoma

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 w...

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Detalles Bibliográficos
Autores: Capdevila Castillón, Jaume|||0000-0003-0718-8619, Wirth, Lori J., Ernst, Thomas, Ponce Aix, Santiago|||0000-0002-2289-4709, Lin, Chia-Chi|||0000-0002-2573-5789, Ramlau, Rodryg, Butler, Marcus O., Delord, Jean-Pierre, Gelderblom, Hans J|||0000-0001-9270-8636, Ascierto, Paolo A., Fasolo, Angelica, Führer, Dagmar, Hütter-Krönke, Marie Luise, Forde, Patrick M., Wrona, Anna, Santoro, Armando|||0000-0003-1709-9492, Sadow, Peter M., Szpakowski, Sebastian, Wu, Hongqian, Bostel, Geraldine, Faris, Jason, Cameron, Scott, Varga, Andreea, Taylor, Matthew
Tipo de recurso: informe técnico
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:248876
Acceso en línea:https://ddd.uab.cat/record/248876
https://dx.doi.org/urn:doi:10.1200/JCO.19.02727
Access Level:acceso abierto
Descripción
Sumario: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. 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. 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. To our knowledge, this is the first clinical trial to show responsiveness of anaplastic thyroid carcinoma to PD-1 blockade.

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