Background  Nowadays, immune checkpoint inhibitors (ICIs) have become standard first-line and third-line therapeutics in advanced gastric cancer. But in second-line therapy, they are only recommended for patients with microsatellite instability -high(MSI-H) or mismatch repair gene defects. Therefore, the treatment mode of ICIs in the second-line of advanced gastric cancer needs more exploration.

  Objective  To analyze the efficacy of ICIs combined with chemotherapy and antiangiogenic drug in the treatment of advanced gastric cancer and gastroesophageal junction cancer.

  Methods  Clinical data about patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma who received ICIs combined with chemotherapy and antiangiogenic drug in the second line of the First Medical Center of Chinese PLA General Hospital from June 2018 to January 2022 were collected. Median progression-free survival (mPFS), objective response rate (ORR) and disease control rate (DCR) of enrolled patients were analyzed. Kaplan-Meier method was used to plot the survival curve, and COX regression was used to analyze the prognostic factors affecting mPFS.

  Results  A total of 49 patients with a median age of 54 years were included in this study, including 34 males and 15 females. In second-line therapy, ICIs were either nivolumab or sintilimab, with 27 patients receiving nivolumab and 22 patients receiving sintilimab. There were 28 patients combined with albumin bound paclitaxel, 21 cases with apatinib, 6 case with platinum-based regimen, and 5 case with irinotecan-based regimen. About 69.4% of the patients chose immuno-therapy combined with ≥2 antitumor drugs. The ORR was 28.5%, DCR was 89.8%, mPFS was 4.7 (95% CI: 3.830-5.570) months. Multivariate Cox analysis showed that mPFS in patients without peritoneal metastasis was significantly better than that in patients with peritoneal metastasis (HR=0.410, 95% CI: 0.197-0.854, P=0.017); patients who did not receive first-line immunotherapy were signifi-cantly better than those receiving first-line immunotherapy (HR=0.518, 95% CI: 0.272-0.987, P=0.045), and patients with a second-line combination of ≥2 drugs had significantly better PFS prognosis than those with a combination of one drug (HR=0.454, 95% CI: 0.231-0.890, P=0.021).

  Conclusion  ICIs combined with chemotherapy or antiangiogenic drugs as second-line therapy may improve the effective rate and prolong the PFS of patients with advanced gastric cancer and gastroesophageal junction adenocarcinoma.