Our findings also support a pragmatic selection of second‐ or later‐line treatment (combining ICIs with either anti‐angiogenesis agents or chemotherapy) to balance clinical efficacy, safety, and resource availability because PD‐1 inhibitor combined with anti‐angiogenesis therapy or chemotherapy showed high antitumor activity in both immunotherapy‐naive and immunotherapy‐treated advanced ESCC patients. Here, PDCD1 is linked to esophageal squamous cell carcinoma.