Changes in the neutrophil-to-lymphocyte ratio (NLR) as predictive values for metastatic gastric cancer patients with PD-1 inhibitors

Abstract

BackgroundThe combination of immunotherapy and chemotherapy can improve the survival of metastatic gastric cancer (MGC) patients based on checkmate 649 and Orential 16. The neutrophil-to-lymphocyte ratio (NLR) in the pretreatment period can be used as a prognostic indicator in patients receiving immune checkpoint inhibitors (ICIs) to treat different cancers. However, no study has yet explored the relationships between NLR changes during PD-1 treatment and patient survival.MethodFirst, we enrolled patients diagnosed with MGC under anti-PD-1-based treatments from October 1st, 2015 to December 31st, 2020 at the Chinese PLA General Hospital. These patients were stratified regarding their baseline NLR and variants of NLR. Then we explored the association between relative NLR changes and other clinical features with the overall survival (OS) and progression-free survival (PFS) of patients treated with immunotherapy using multivariate Cox analysis.ResultsA total of 137 patients were enrolled in the present study. We categorized patients into decreased (ΔNLR < 0) and increased (ΔNLR ≥ 0) post-treatment NLR groups. The median OS and PFS were 12.3 months and 7.8 months for patients with ΔNLR < 0, respectively, compared to 7.5 months and 4.3 months for patients with ΔNLR ≥ 0 (both p < 0.05). The ORR was 41.8% in the ΔNLR < 0 group, higher than the ΔNLR ≥ 0 group (ORR = 24.3%). Patients with both NLR ≥ 3.23 and ΔNLR ≥ 0 had a significantly increased risk of death (HR: 2.349, 95% CI: 1.701 – 3.243, p < 0.001) and disease progression (HR: 2.297, 95% CI: 1.666 – 3.167, p < 0.001) compared to patients with NLR < 3.23 and ΔNLR < 0. Patients with either NLR ≥ 3.23 or ΔNLR ≥ 0 showed an intermediate risk of death (HR: 2.626, 95% CI: 1.660 – 4.155, p < 0.001) and progression (HR: 2.554, 95% CI: 1.590 – 4.101, p < 0.001). The ORR (50.0%) and DCR (91.2%) was higher in the NLR < 3.23 and ΔNLR < 0 group compared to other combination groups (both p < 0.05).ConclusionThe combination of NLR changes after anti-PD-1 treatment with the baseline NLR was significantly correlated with patient survival and could be used to categorize patients into high- and low-risk groups. Finally, prospectively designed clinical trials are required to substantiate our current findings.