Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2)
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Published:2022-02-14
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Xu JianmingORCID, Li Yi, Fan Qingxia, Shu Yongqian, Yang Lei, Cui Tongjian, Gu Kangsheng, Tao Min, Wang Xiuwen, Cui Chengxu, Xu Nong, Xiao Juxiang, Gao Quanli, Liu Yunpeng, Zhang Tao, Bai Yuxian, Li Wei, Zhang Yiping, Dai Guanghai, Ma Dong, Zhang Jingdong, Bai Chunmei, Huang Yunchao, Liao WangjunORCID, Wu Lin, Chen Xi, Yang Yan, Wang Junye, Ji Shoujian, Zhou Hui, Wang Yan, Ma Zhuo, Wang Yanqi, Peng Bo, Sun Jiya, Mancao Christoph
Abstract
AbstractThis randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.2 vs.6.2 months;P = 0.032; HR = 0.70; 95% CI, 0.50–0.97). Incidence of treatment-related adverse events of grade 3–5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1%). Patients with high T-cell receptor (TCR) clonality and low molecular tumor burden index (mTBI) showed the longest median OS (15.0 months). Patients with NLR < 3 at 6 weeks post-treatment had a significantly prolonged median OS (16.6 months) compared with NLR ≥ 3. The results demonstrate a significant improvement in OS of sintilimab compared to chemotherapy as second-line treatment for advanced or metastatic ESCC.
Funder
National Natural Science Foundation of China This study was supported by Innovent Biologics, Inc., and co-funded by Eli Lilly and Company.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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