Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma

Guozhen Yang; Xiaodong Su; Hong Yang; Guangyu Luo; Chan Gao; Yating Zheng; Wenzhuan Xie; Mengli Huang; Ting Bei; Yuezong Bai; Zhiqiang Wang; Peiqiang Cai; Haoqiang He; Jin Xiang; Muyan Cai; Yijun Zhang; Chunhua Qu; Jianhua Fu; Qianwen Liu; Yi Hu; Jiudi Zhong; Yuanheng Huang; Qiyu Guo; Xu Zhang

doi:10.21037/atm-21-3352

Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma

Ann Transl Med. 2021 Aug;9(15):1254. doi: 10.21037/atm-21-3352.

Authors

Guozhen Yang^{1

2

3}, Xiaodong Su^{1

2

3}, Hong Yang^{1

2

3}, Guangyu Luo^{1

4}, Chan Gao⁵, Yating Zheng⁵, Wenzhuan Xie⁵, Mengli Huang⁵, Ting Bei⁵, Yuezong Bai⁵, Zhiqiang Wang^{1

6}, Peiqiang Cai^{1

7}, Haoqiang He^{1

7}, Jin Xiang^{1

8}, Muyan Cai^{1

8}, Yijun Zhang^{1

8}, Chunhua Qu^{1

8}, Jianhua Fu^{1

2

3}, Qianwen Liu^{1

2

3}, Yi Hu^{1

2

3}, Jiudi Zhong^{1

2

3}, Yuanheng Huang^{1

2

3}, Qiyu Guo^{1

2

3}, Xu Zhang^{1

2

3}

Affiliations

¹ State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
² Guangdong Esophageal Cancer Institute, Guangzhou, China.
³ Department of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁴ Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁵ Medical Affairs, 3D Medicines, Inc., Shanghai, China.
⁶ Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁷ Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁸ Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Abstract

Background: Immunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.

Methods: Patients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.

Results: Twelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).

Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.

Keywords: Anti-programmed death-1 (PD-1); esophageal squamous cell carcinoma (ESCC); neoadjuvant therapy; tumor immune microenvironment (TIME); tumor mutational burden (TMB).