Abstract

BackgroundOptimal prognostic biomarkers for patients with gastric cancer who received immune checkpoint inhibitor (ICI) are lacking. Inflammatory markers including lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII) are easily available. However, its correlation with ICI is unknown in gastric cancer. Here, we evaluated the potential association between LMR, PLR, and SII with clinical outcomes in gastric cancer patients undergoing ICI therapy.MethodsWe examined LMR, PLR, SII at baseline, and 6 (± 2) weeks later in 139 patients received ICI therapy between August 2015 and April 2019 at Peking University Cancer Hospital (Beijing, China). Landmark analysis at 6 weeks was conducted to explore the prognostic value of LMR, PLR, and SII on progress-free survival (PFS), and overall survival (OS). A Cox proportional hazards model was used to compute mortality hazard ratios (HRs) for LMR, adjusting for potential confounders including age, sex, ECOG, tumor location, tumor differentiation, tumor stage, line of therapy, and type of anti-PD-1/PD-L1 therapy.ResultsAmong 139 patients, 103 (74.1%) were male, median age was 60 years. Median duration of therapy was 6 cycles. We observed that both LMR at baseline and week 6 were independent prognostic factors. Patients with a higher LMR (≥ 3.5) at baseline or week 6 had superior PFS [baseline: HR 0.58, 95% confidence interval (CI): 0.38–0.91; week 6: HR 0.48, 95% CI: 0.29–0.78] and OS (baseline: HR 0.38, 95% CI: 0.24–0.62; week 6: HR 0.52, 95% CI: 0.31–0.88) compared with patients with a lower LMR (< 3.5). Furthermore, for patients with both LMR ≥ 3.5 at baseline and LMR ≥ 3.5 at week 6 were estimated to have much better PFS (HR 0.41, 95% CI: 0.23–0.72) and OS (HR 0.34, 95% CI: 0.18–0.64) than patients with both LMR < 3.5 at baseline and LMR < 3.5 at week 6.ConclusionsBaseline and early changes in LMR were strongly associated with survival in gastric cancer patients who received ICI therapy, and may serve to identify patients most likely to benefit from ICI.

Highlights

  • Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer death worldwide, especially with a high incidence in East Asia [1]

  • Immune checkpoint inhibitors (ICI) elicits durable antitumor effects, immunotherapy could cause serious toxicities and high treatment cost, there is an urgent need to identify patients most likely to benefit from ICI [5]

  • Previous studies reported that microsatellite instability-high (MSI-H) and EpsteinBarr virus (EBV)-positive gastric cancer prone to have a better response from ICI therapy, but there appear to be a significant portion of patients who do benefit from immunotherapy with microsatellite stable (MSS) or EBV-negative status [12]

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Summary

Introduction

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer death worldwide, especially with a high incidence in East Asia [1]. Higher tumor mutation burden (TMB) has been correlated with better ORR and superior overall survival (OS) in patients treated with pembrolizumab in KEYNOTE-061 trial [11]. Both PD-L1 expression and TMB are limited by dynamic changes over treatment, tumor heterogeneity and different test methods. Previous studies reported that microsatellite instability-high (MSI-H) and EpsteinBarr virus (EBV)-positive gastric cancer prone to have a better response from ICI therapy, but there appear to be a significant portion of patients who do benefit from immunotherapy with microsatellite stable (MSS) or EBV-negative status [12]. We evaluated the potential association between LMR, PLR, and SII with clinical outcomes in gastric cancer patients undergoing ICI therapy

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