Comparative efficacy of treatments for previously treated patients with advanced esophageal and esophagogastric junction cancer: A network meta-analysis.

BACKGROUND:It remains unclear which treatment is the most effective for previously treated patients with advanced esophageal and esophagogastric junction (EGJ) cancer. We conducted a network meta-analysis to address this important issue. METHODS:PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant phase II and III randomized controlled trials (RCTs). Overall survival (OS) was the primary outcome of interest, which was reported as hazard ratio (HR) and 95% confidence intervals (CIs). RESULTS:Sixteen RCTs involving 3372 patients and evaluating 15 treatments were included in this network meta-analysis. Ramucirumab+chemotherapy (CT) (HR = 0.52, 95% CI: 0.35-0.77) and use of programmed death receptor 1 (PD-1) inhibitors, including camrelizumab (HR = 0.71, 95% CI: 0.57-0.88), sintilimab (HR = 0.70, 95% CI: 0.50-0.98), nivolumab (HR = 0.76, 95% CI: 0.62-0.94), and pembrolizumab (HR = 0.84, 95% CI: 0.72-0.98), conferred better OS than CT; however, this OS benefit was not observed for PD-L1 inhibitor (avelumab) and other target agents (trastuzumab, everolimus, gefitinib, and anlotinib). In subgroup analysis, ramucirumab+CT and pembrolizumab showed significant improvement in OS, when compared to CT, in esophageal/EGJ adenocarcinoma (AC) cases; moreover, all PD-1 inhibitors had significant OS advantage over CT in treating esophageal squamous cell carcinoma (SCC). Based on treatment ranking in terms of OS, ramucirumab+CT and camrelizumab were ranked the best treatments for patients with AC and SCC, respectively. CONCLUSIONS:Ramucirumab+CT and PD-1 inhibitors were superior to CT for previously treated cases of advanced esophageal/EGJ cancer. Ramucirumab+CT seemed to be the most effective treatment in patients with esophageal/EGJ AC, while use of PD-1 inhibitors, especially camrelizumab, was likely to be the optimal treatment in patients with esophageal SCC.