TY - JOUR
T1 - PD-1 blockade in anaplastic thyroid carcinoma
AU - Capdevila, Jaume
AU - Wirth, Lori J.
AU - Ernst, Thomas
AU - Aix, Santiago Ponce
AU - Lin, Chia Chi
AU - Ramlau, Rodryg
AU - Butler, Marcus O.
AU - Delord, Jean Pierre
AU - Gelderblom, Hans
AU - Ascierto, Paolo A.
AU - Fasolo, Angelica
AU - Führer, Dagmar
AU - Hütter-Krönke, Marie Luise
AU - Forde, Patrick M.
AU - Wrona, Anna
AU - Santoro, Armando
AU - Sadow, Peter M.
AU - Szpakowski, Sebastian
AU - Wu, Hongqian
AU - Bostel, Geraldine
AU - Faris, Jason
AU - Cameron, Scott
AU - Varga, Andreea
AU - Taylor, Matthew
N1 - Funding Information:
Supported by Novartis Pharmaceuticals.
Funding Information:
We thank the patients who participated in the trial and their families and thank the physicians, nurses, research coordinators, and other staff at each site who assisted with the study. We also thank Jennifer Mataraza, Victor Antona, Antonio Silva, and Emilie Bossuge for their contributions to this study. Editorial assistance was provided by Laura Hilditch, PhD, and was funded by Novartis Pharmaceuticals.
Publisher Copyright:
© 2020 by American Society of Clinical Oncology.
PY - 2020/8
Y1 - 2020/8
N2 - 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 5 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.
AB - 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 5 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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U2 - 10.1200/JCO.19.02727
DO - 10.1200/JCO.19.02727
M3 - Article
C2 - 32364844
AN - SCOPUS:85087317668
SN - 0732-183X
VL - 38
SP - 2620
EP - 2627
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 23
ER -