Abstract

PurposeThis clinical study sought to determine whether the levels of inflammatory markers predicted the survival of advanced gastric cancer (AGC) patients who underwent anti-programmed death 1 (PD-1) therapy.MethodsUsing AGC patient plasma samples and baseline characteristics, we investigated the specific value of inflammatory markers in AGC from a clinical perspective in immunotherapy.ResultsOne hundred and six patients with AGC who underwent anti-PD-1 therapy were enrolled in this study between 20 July 2019 and 16 March 2021. A significant decrease in NLR, dNLR, and SII was noticed among the PR (P=0.023; P=0.036; P=0.001), SD (P=0.048; P=0.022; P=0.023), ORR (P=0.021; P=0.032; P=0.001), and DCR (P=0.003; P=0.001; P<0.001) groups after anti-PD-1 therapy. Additionally, a significant decline of PLR was also observed in PR (P=0.010), ORR (P=0.007), and DCR (P=0.005) after anti-PD-1 therapy. Only MLR levels increased significantly at the time of anti-PD-1 immunotherapy the failure compared to baseline (P=0.039). And statistically significant elevations in NLR (P=0.001), MLR (P=0.020), dNLR (P=0.002), and SII (P=0.019) were found in failure of anti-PD-1 treatment compared to optimal efficacy in AGC patients. In first-line treatment, the number of metastatic sites (P=0.001) was an independent prognostic factor for PFS, and peritoneal metastases (P=0.004) and platelet-to-lymphocyte ratio (PLR) level (P=0.014) were independent prognostic predictors of OS according to Cox regression analysis. In second-line or posterior treatment, the number of metastatic sites (P=0.007), ECOG (P=0.011), and PLR level (P=0.033) were independent prognostic factors for PFS in AGC patients, and the number of metastatic sites (P=0.003), differentiation (P=0.030), and NLR level (P<0.001) were independent prognostic factors for OS according to Cox regression analysis.ConclusionsNLR, PLR, MLR, dNLR, and SII can reflect the short-term efficacy of immunotherapy in patients who underwent anti-PD-1 therapy with AGC. PLR is an independent prognostic factor for OS in AGC patients receiving first-line immunotherapy and PFS in those receiving second-line or posterior immunotherapy. And NLR was an independent prognostic factor for OS in AGC patients receiving second-line or posterior immunotherapy. The number of metastatic sites was significantly associated with the prognosis of AGC patients who received immunotherapy.

Highlights

  • Gastric carcinoma is one of the most prevalent malignancies

  • A significant decrease in neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and SII was noticed among the partial response (PR) (P=0.023; P=0.036; P=0.001), SD (P=0.048; P=0.022; P=0.023), objective response rate (ORR) (P=0.021; P=0.032; P=0.001), and disease control rate (DCR) (P=0.003; P=0.001; P

  • In second-line or posterior treatment, the number of metastatic sites (P=0.007), ECOG (P=0.011), and platelet-tolymphocyte ratio (PLR) level (P=0.033) were independent prognostic factors for progression-free survival (PFS) in advanced gastric cancer (AGC) patients, and the number of metastatic sites (P=0.003), differentiation (P=0.030), and NLR level (P

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Summary

Introduction

Gastric carcinoma is one of the most prevalent malignancies. It remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally [1], and it is typically diagnosed at an advanced stage. Immuno-oncological agents targeting PD-1 have shown promising results against several cancer types, such as malignant melanoma [4], non-small cell lung cancer [5], and oesophageal carcinoma [6]. According to the results of the ATTRACTION-2 trial [7], nivolumab significantly improved the survival of AGC patients who received two or more lines of therapy. CheckMate 649 trials showed that in patients with strong PD-L1 positivity (CPS≥5), nivolumab plus chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in comparison with chemotherapy alone [8]. Multiple anti-PD-1 therapy clinical trials are underway or have been completed

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