Immune checkpoint inhibitors in patients with advanced gastric cancer: a multi-institutional retrospective real-world study

Aim: Selecting patients for immunotherapy in metastatic gastric cancer (mGC) in second and subsequent lines remains challenging. The aim of our study is to assess the feasibility of anti-programmed death-ligand 1 (anti-PD-L1) inhibitors in pretreated patients with mGC, and to determine prognostic and predictive biomarkers. Methods: We retrospectively analyzed data of 122 patients treated in five oncology centers in Moscow between 2018 and 2023, who received nivolumab or pembrolizumab for advanced gastric cancer. The primary end-point of our study was 6-month progression-free survival (PFS). For multivariate analysis, variables with a value of p < 0.05 obtained in a univariate analysis were selected. The optimal threshold value of the neutrophil-lymphocyte ratio (NLR) as a predictor of the effectiveness of immunotherapy was determined using receiver operating characteristic (ROC) curve analysis. Results: Patients with mGC who received immune checkpoint inhibitors (ICIs) were included. 6-month PFS rate was 31.6%. The median PFS (mPFS) and overall survival (mOS) in patients in the high NLR group (NLR ≥ 1.8) were 2 and 4 months; mOS and mPFS in the low NLR group were not achieved (p < 0.001). The presence of ascites (p < 0.001), the administration of ICIs in III–IV lines (p = 0.004), and NLR ≥ 1.8 (p = 0.006) were independent prognostic factors, associated with decrease of OS. The median OS of patients in favorable and unfavorable prognostic groups were 13 months and 2 months, respectively (p < 0.001). Conclusions: Ascites, NLR level of ≥ 1.8, and administration of anti-PD-L1 inhibitors were associated with low efficacy of immunotherapy in patients with microsatellite stable mGC. Further research should be planned including patients who did not receive ICIs to determine the prognostic significance of our model.