Abstract
Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64–1.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy.
Highlights
Gastric cancer (GC) accounted for over 1,000,000 new cases in 2018 with an estimated 783,000 deaths, making it the fifth most common cancer worldwide and the third leading cause of cancer deaths [1]
The treatment of several tumours has been revolutionized by the introduction of immune checkpoint inhibitors (ICIs) [17], and for this reason, they have been evaluated in metastatic GC
The here-presented meta-analysis, including three randomised controlled trials (RCTs) with a total of 1456 pre-treated metastatic GC patients, and targeted with ICIs, suggests that there is no statistically significant improvement in overall survival (OS), and no advantage in terms of PFS and tumour response rate. Since this meta-analysis analysed only three RCTs, it is not possible to conclude that ICIs do not work in pre-treated metastatic GC
Summary
Gastric cancer (GC) accounted for over 1,000,000 new cases in 2018 with an estimated 783,000 deaths, making it the fifth most common cancer worldwide and the third leading cause of cancer deaths [1]. No standard treatment is recommended by guidelines for patients who failed two or more lines of therapy, two drugs, apatinib (a tyrosine kinase inhibitor that selectively inhibits VEGFR2) and trifluridine/tipiracil (TAS-102), were shown to increase survival when compared to a placebo as third-line or later therapy for advanced GC [6,7]. Based on the results of a phase II study [12], pembrolizumab (an anti-PD-1 ICI) has been approved by the food and drug administration (FDA) for the treatment of patients with recurrent locally advanced or metastatic GC whose tumours express PD-L1. In the following phase III trial, no remarkable overall survival (OS) outcomes have been reported with pembrolizumab when compared with paclitaxel as a second-line regimen in PD-L1-positive advanced gastric cancer or gastro-oesophageal junction cancer [13]. We performed a meta-analysis to evaluate the impact of ICIs on the outcomes of patients with metastatic GC focusing on the possible predictor of efficacy
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