Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma

被引:174
作者
Yang, Weixiong [1 ]
Xing, Xiangbin [2 ]
Yeung, Sai-Ching Jim [3 ]
Wang, Siyu [4 ,5 ]
Chen, Wenfang [6 ]
Bao, Yong [7 ]
Wang, Fang [8 ]
Feng, Shiting [9 ]
Peng, Fang [7 ]
Wang, Xiaoyan [10 ]
Chen, Shuling [11 ]
He, Minghui [12 ]
Zhang, Ning [2 ]
Wang, Honglei [6 ]
Zeng, Bo [1 ]
Liu, Zhenguo [1 ]
Kidane, Biniam [13 ]
Seder, Christopher W. [14 ]
Koyanagi, Kazuo [15 ]
Shargall, Yaron [16 ]
Luo, Honghe [1 ]
Peng, Sui [8 ,17 ]
Cheng, Chao [1 ]
机构
[1] Sun Yat Sen Univ, Dept Thorac Surg, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Dept Gastroenterol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[3] Univ Texas MD Anderson Canc Ctr, Dept Emergency Med, Houston, TX 77030 USA
[4] Sun Yat Sen Univ Canc Ctr, Dept Thorac Surg, Guangzhou, Guangdong, Peoples R China
[5] Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China
[6] Sun Yat Sen Univ, Dept Pathol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[7] Sun Yat Sen Univ, Dept Radiotherapy, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[8] Sun Yat Sen Univ, Inst Precis Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[9] Sun Yat Sen Univ, Dept Radiol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[10] Sun Yat Sen Univ, Dept Nucl Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[11] Sun Yat Sen Univ, Div Intervent Ultrasound, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[12] Sun Yat Sen Univ, Dept Liver Surg, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
[13] Univ Manitoba, Max Rady Coll Med, Dept Surg, Winnipeg, MB, Canada
[14] Rush Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, Chicago, IL USA
[15] Tokai Univ, Dept Gastroenterol Surg, Sch Med, Isehara, Kanagawa, Japan
[16] McMaster Univ, Div Thorac Surg, St Josephs Healthcare Hamilton, Hamilton, ON, Canada
[17] Sun Yat Sen Univ, Clin Trials Unit, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
关键词
immunotherapy; clinical trials as topic; drug therapy; combination; tumor microenvironment; therapies; investigational; LUNG-CANCER; PREOPERATIVE CHEMORADIOTHERAPY; OPEN-LABEL; IMMUNOSUPPRESSION; MULTICENTER; MACROPHAGES; REGRESSION; SURVIVAL;
D O I
10.1136/jitc-2021-003497
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Programmed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC. Methods Patients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6-9 weeks after the first cycle. Results Between January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3-4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1(+) CD163(+) cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017). Conclusions Neoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC.
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页数:11
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