Efficacy and Safety of Immune Checkpoint Inhibitor in Advanced Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Abstract

BackgroundThe published evidence from several randomized controlled clinical trials of immunotherapy for advanced esophageal squamous cell carcinoma has shown promising results. This study aimed to investigate the efficacy and safety of immune checkpoint inhibitor treatment in esophageal squamous cell carcinoma.MethodsPubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published before December 30, 2020. The data for efficacy and safety of immune checkpoint inhibitor treatment were subjected to meta-analysis.ResultsSeven clinical trials comprising 1733 patients were included. The results showed that immune checkpoint inhibitor treatment as second- or later-line treatment was associated with an increased risk of the objective response rate (relative risk: 1.82, 95% confidence interval: 0.82–4.04; P=0.002) and median overall survival (hazard ratio: 0.75, 95% confidence interval: 0.67–0.85; P<0.001) compared with chemotherapy in locally advanced or metastatic esophageal squamous cell carcinoma. Moreover, immune checkpoint inhibitor treatment was associated with significant improvement in median overall survival (hazard ratio: 0.61, 95% confidence interval: 0.48–0.77, P<0.001) compared with chemotherapy in the programmed death-ligand 1 (PD-L1)-positive population. However, immune checkpoint inhibitor treatment was also effective in all patients independent of PD-L1 expression. The most common grade ≥3 treatment-related adverse events with immune checkpoint inhibitor therapy were anemia, asthenia, rash, fatigue, decreased appetite, diarrhea, pneumonia, decreased neutrophil count, and vomiting. Patients undergoing immune checkpoint inhibitor therapy was associated with a decreased risk of treatment-related adverse events (relative risk: 0.82, 95% confidence interval: 0.62–1.08; P<0.001) and grade ≥3 treatment-related adverse events (relative risk: 0.50, 95% confidence interval: 0.42–0.60; P<0.001) compared with those undergoing chemotherapy.ConclusionsImmune checkpoint inhibitors as second- or later-line therapy may improve overall response rate and overall survival but not all oncological outcomes for patients with locally advanced or metastatic esophageal squamous cell carcinoma. Patients treated with immune checkpoint inhibitors might experience fewer treatment-related adverse events of any grade, but specifically grade ≥3, compared with those treated with chemotherapy.

Multi‐omics analyses reveal spatial heterogeneity in primary and metastatic oesophageal squamous cell carcinoma

“…Although ICB has revolutionised ESCC therapeutics, not all patients gain clinical benefits from these treatments, 50 which raises the question of whether the spatial ITH is responsible for these differences. This study utilised emerging DSP technology to address the AOIs of specific tumours and stroma and to assess the fundamental molecular nature of our ESCC cohort.…”

“…Unprecedented advances have been made in ESCC treatment with the application of immune checkpoint blockade (ICB). 49,50 However, immunomodulators and the immune cell repertoire have not been well characterised in ESCC, particularly in the subregions of the primary tumour (PT sup and PT deep ) and matched LN met . First, we focused on the expression of the 33 immunomodulatory genes associated with cancer immunity (Table S12).…”

Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China

“…Cancer treatment requires ongoing monitoring and flexible strategies, which might be lacking in these lower-tier institutions. 59,60 Nonetheless, the 37.5% discount could benefit patients with mobility issues, those living in remote locations, or those without insurance coverage for this treatment, as they might opt for a more affordable medication and comprehensive treatment at primary health care institutions.…”

Advances in immunotherapy for metastatic esophageal cancer

“…e most common Grade ≥3 treatment-related adverse events (TRAEs) were anemia, asthenia, rash, fatigue, anorexia, diarrhea, pneumonia, neutropenia, and vomiting. Patients receiving ICIs had a decreased risk of TRAEs (relative risk: 0.82, 95% CI: 0.62-1.08; P < 0.001) and Grade ≥3 TRAEs (RR: 0.50, 95% CI: 0.42-0.60; P < 0.001) compared with those undergoing CT. [26] IO IN SUBSEQUENT LINES e large Phase 2 expansion cohort of the KEYNOTE-059 trial reported results for pembrolizumab in 259 patients with gastric or EGJ adenocarcinoma. is international multicenter trial enrolled equal proportions of patients with gastric (48.3%) and EGJ cancers (51.4%).…”