The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis

Wenwu He; Chenghao Wang; Changding Li; Xin Nie; Haojun Li; Jialong Li; Na Zhao; Haijun Chen; Xiaojie Miao; Yongtao Han; Lin Peng; Xuefeng Leng

doi:10.3389/fimmu.2023.1118902

The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis

Front Immunol. 2023 Feb 17:14:1118902. doi: 10.3389/fimmu.2023.1118902. eCollection 2023.

Authors

Wenwu He¹, Chenghao Wang¹, Changding Li¹, Xin Nie¹, Haojun Li¹, Jialong Li¹, Na Zhao², Haijun Chen², Xiaojie Miao², Yongtao Han¹, Lin Peng¹, Xuefeng Leng¹

Affiliations

¹ Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China, Chengdu, China.
² Medical Affairs Department of BeiGene (Beijing) Co., Ltd, Beijing, China.

Abstract

Objective: This systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC).

Background: Several studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking.

Methods: Studies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0.

Results: Thirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26-0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31-0.65; nICT: 0.29, 95% CI: 0.26-0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1-2 and 3-4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56-0.84) and 0.16 (95% CI: 0.09-0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3-4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17-0.77; nICT: 0.14, 95% CI: 0.07-0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15-0.53; cisplatin: 0.04, 95% CI: 0.01-0.09; p<0.01).

Conclusion: Neoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.

Keywords: esophageal squamous cell carcinoma; meta-analysis; nICRT; nICT; neoadjuvant immunotherapy.

Publication types

Meta-Analysis
Systematic Review
Review
Research Support, Non-U.S. Gov't

MeSH terms

Carboplatin
Cisplatin
Esophageal Neoplasms*
Esophageal Squamous Cell Carcinoma*
Humans
Immunotherapy
Neoadjuvant Therapy

Substances

Carboplatin
Cisplatin

Grants and funding

This work was funded by Sichuan Science and Technology Program (2020YFH0169, 23ZDYF2430); Sichuan Province Clinical Key Specialty Construction Project and Bethune Charitable Foundation (HZB-20190528-19).