Decrease in tumor content assessed in biopsies is associated with improved treatment outcome response to pembrolizumab in patients with rare tumors

作者：Coya Tapia, Phyu P. Aung, Sinchita Roy‐Chowdhuri, Mingxuan Xu, Fengying Ouyang, Anas Alshawa, Joud Hajjar, Gopal K. Singh, Vincent W. Yang, Lilibeth Castillo, Hung Dinh Le, RAVI K. MURTHY, Bettzy Stephen, Kenneth R. Hess, Ignacio Ivan Wistuba, Aung Naing · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2020 · DOI：10.1136/jitc-2020-000665 · 被引用次数：12 · 研究领域：Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research、Esophageal Cancer Research and Treatment

BACKGROUND: Decreased tumor content (TC) in resection specimens after neoadjuvant therapy is used to predict prognosis. We investigated whether TC assessed in biopsy specimens or the shift in TC from baseline to on-treatment can be used accordingly to predict response in patients with rare tumors who were treated with pembrolizumab. METHODS: A total of 57 tumors (represented by 173 baseline and 179 on-treatment biopsies) from 57 patients with rare tumors participating in an ongoing phase II clinical trial of pembrolizumab were evaluated. TC was estimated on H&E-stained slides and tumors were dichotomized into low and high TC according to a cut-off of 10%. Necrosis, proliferative fibrosis (PF) and normal tissue were assessed in on-treatment biopsies. TC at baseline and on-treatment, as well as the shift in TC from baseline to on-treatment, was correlated with clinical response defined according to Response Evaluation Criteria in Solid Tumors. RESULTS: A decrease in TC was seen in 14% (n=8); no change in TC was seen in 75% (n=43); and an increase in TC from baseline to on-treatment was seen in 11% (n=6). Objective response was significantly associated with decrease in TC from baseline to on-treatment (38%, 3/8) compared with no change/increase in TC (6%, 3/49) (p=0.031). Patients with a decrease in TC had a significantly increased time to progression (TTP) (75% probability) compared with patients with an increase (20% probability) or no change in TC (19% probability) (p=0.0042)...