In the published data from five multicenter RCTs with 1970 advanced ESCC patients, our pooled analysis revealed that PD-1 inhibitors as second-line therapy resulted in better OS and ORR in advanced ESCC patients than chemotherapy, especially significantly prolonged OS in patients with positive PD-L1 status, and were associated with a lower incidence of grade 3–5 TRAEs. Here, CD274 is linked to esophageal squamous cell carcinoma.