Abstract
Patients with advanced gastroesophageal cancer refractory to the previous regimen of chemotherapy suffered from poor prognosis without many effective treatment options. Immune checkpoint inhibitors (ICIs) provide promising efficacy, but the relevant clinical trials have offered controversial data. We performed this meta-analysis to compare the efficacy and safety of inhibitors against programmed cell death receptor 1 (PD-1) and its ligand PD-L1 versus chemotherapy as second or third-line therapy in patients with advanced gastroesophageal cancer. Six randomized controlled trials (RCTs) including 2,648 patients were included. The meta-analysis results indicated that both ORR (RR = 1.39, 95% CI: 0.85∼2.25, P = 0.188) and PFS (HR = 1.14, 95% CI: 0.88∼1.46, P = 0.316) were not significantly improved by ICIs compared with chemotherapy. However, the OS was significantly prolonged (HR = 0.85, 95% CI: 0.75–0.97, P = 0.018) in the ICIs group compared with chemotherapy. Subgroup analysis showed that ICIs provide statistically significant OS benefits over chemotherapy in PD-L1-positive, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and aged 65 or older patients. Compared with chemotherapy, the TRAEs risk of ICIs was reduced by 33% (RR = 0.67, 95% CI: 0.62–0.73, P ≤ 0.001). And the risk of grades 3–5 of TRAEs was reduced by 60% (RR = 0.40, 95% CI: 0.33–0.49, P ≤ 0.001). Compared to chemotherapy, ICIs appeared to improve OS and were better tolerated in previously treated patients with advanced esophageal cancer. We recommend PD-1/PD-L1 inhibitors as an optimal treatment option for positive PD-L1 expression, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and ≥65 years of age patients.
Highlights
Upper gastrointestinal cancer is one of the leading causes of cancer-related death in the world, with about 1.6 million new cases and 1.3 million deaths in 2018 [1]
It is easy to develop drug resistance and result in disease progression after first-line treatment, while the efficacy of the following chemotherapy regime is not desirable with severe side effects. e patients who have failed in previous regimens are often in poor physical condition and are difficult to bear subsequent treatment. e medicines targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), and vascular endothelial growth factor (VEGF) showed effect on some patients, but the benefits are limited [3]. erefore, how to improve the efficacy of patients with advanced gastroesophageal cancer refractory or intolerant to previous chemotherapy is an urgent problem
Studies eligible for inclusion met all of the following criteria: (1) patients were clinically diagnosed as advanced esophageal cancer (EC)/gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and progressed after the failure of one or more chemotherapy regimens; (2) the trial group was treated with a single PD-1/ PD-L1 inhibitor; (3) the control group was treated with chemotherapy; (4) the outcome index included clinical efficacy and survival analysis judged by RECIST criteria, and Treatment-Related Adverse Events (TRAEs) were classified and graded; and (5) prospective RCTs
Summary
Upper gastrointestinal cancer is one of the leading causes of cancer-related death in the world, with about 1.6 million new cases and 1.3 million deaths in 2018 [1]. Because of concealed incidence and rapid development, the prognosis of gastroesophageal cancer is really poor. Most of the patients tend to be diagnosed at advanced stages and lost the opportunity for operation. For these patients with advanced gastroesophageal cancer, combined chemotherapy based on 5fluorouracil and platinum is the standard first-line treatment [2]. It is easy to develop drug resistance and result in disease progression after first-line treatment, while the efficacy of the following chemotherapy regime is not desirable with severe side effects. Erefore, how to improve the efficacy of patients with advanced gastroesophageal cancer refractory or intolerant to previous chemotherapy is an urgent problem. A number of clinical trials have shown that immune checkpoint inhibitors, represented by PD-1/PD-L1 inhibitors, exerted their
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