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)
Jianming Xu, Yi Li, Qingxia Fan, Yongqian Shu, Lei Yang, Tongjian Cui, Kangsheng Gu, Min Tao, Xiuwen Wang, Chengxu Cui, Nong Xu, Juxiang Xiao, Quanli Gao, Yunpeng Liu, Tao Zhang, Yuxian Bai, Wei Li, Yiping Zhang, Guanghai Dai, Dong Ma, Jingdong Zhang, Chunmei Bai, Yunchao Huang, Wangjun Liao, Lin Wu, Xi Chen, Yan Yang, Junye Wang, Shoujian Ji, Hui Zhou, Yan Wang, Zhuo Ma, Yanqi Wang, Bo Peng, Jiya Sun, Christoph Mancao, Jianming Xu, Yi Li, Qingxia Fan, Yongqian Shu, Lei Yang, Tongjian Cui, Kangsheng Gu, Min Tao, Xiuwen Wang, Chengxu Cui, Nong Xu, Juxiang Xiao, Quanli Gao, Yunpeng Liu, Tao Zhang, Yuxian Bai, Wei Li, Yiping Zhang, Guanghai Dai, Dong Ma, Jingdong Zhang, Chunmei Bai, Yunchao Huang, Wangjun Liao, Lin Wu, Xi Chen, Yan Yang, Junye Wang, Shoujian Ji, Hui Zhou, Yan Wang, Zhuo Ma, Yanqi Wang, Bo Peng, Jiya Sun, Christoph Mancao
Abstract
This 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.
Conflict of interest statement
H.Z., Y.W., Z.M., Y.Q.W., B.P., J.Y.S., and C.M. are the staff of Innovent Biologics, Inc. Other authors declare no completing interests.
© 2022. The Author(s).
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