Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer


Ge Fan12,Huo Zhenyu13,Cai Xiuyu4,Hu Qiyuan5,Chen Wenhao6,Lin Guo278,Zhong Ran1,You Zhending2,Wang Rui13,Lu Yi13,Wang Runchen13,Huang Qinhong13,Zhang Haotian3,Song Aiqi3,Li Caichen1,Wen Yaokai9,Jiang Yu13,Liang Hengrui1,He Jianxing1,Liang Wenhua1,Liu Jun1


1. Department of Thoracic Surgery and Oncology, China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

2. First Clinical School, Guangzhou Medical University, Guangzhou, China

3. Nanshan School, Guangzhou Medical University, Guangzhou, China

4. Department of General Internal Medicine, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China

5. The First Clinical Medical School, The First Hospital, Shanxi Medical University, Taiyuan, China

6. School of Basic Medicine, Air Force Medical University, Xi’an, Shaanxi, China

7. Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

8. West China School of Medicine, Sichuan University, Chengdu, China

9. Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China


ImportanceA considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking.ObjectiveTo provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer.Data SourcesPubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022.Study SelectionPublished phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic >50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022.Main Outcomes and MeasuresPathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types.ResultsA total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma.Conclusions and RelevanceThis study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.


American Medical Association (AMA)


General Medicine








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