Comparative Efficacy and Safety of Immunotherapy for Patients with Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Systematic Review and Network Meta-analysis

Background: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Methods We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events. Results Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (cumulative probability, 61%) and PFS (cumulative probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (cumulative probability, 37%) and PFS (cumulative probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively. Conclusions This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC. Trial registration: PROSPERO registration number: (CRD 42021261554).