Systemic inflammatory response and nutritional biomarkers as predictors of nivolumab efficacy for gastric cancer

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ORIGINAL ARTICLE

Systemic inflammatory response and nutritional biomarkers as predictors of nivolumab efficacy for gastric cancer Tsutomu Namikawa1 · Keiichiro Yokota1 · Nobuhisa Tanioka1 · Ian Fukudome1 · Jun Iwabu1 · Masaya Munekage1 · Sunao Uemura1 · Hiromichi Maeda1 · Hiroyuki Kitagawa1 · Michiya Kobayashi2 · Kazuhiro Hanazaki1 Received: 20 February 2020 / Accepted: 13 May 2020 © Springer Nature Singapore Pte Ltd. 2020

Abstract Purpose  To investigate the usefulness of clinicopathological systemic inflammatory response and nutritional biomarkers for predicting the efficacy of nivolumab in patients with advanced gastric cancer. Methods  The subjects of this study were 29 patients who received nivolumab treatment for advanced gastric cancer at the Kochi Medical School between 2017 and 2019. Clinicopathological information, including systemic inflammatory response data, were obtained to investigate the associations between baseline cancer-related prognostic variables and survival outcomes. Results  Immune-related adverse events (irAEs) of any grade were identified in 34.5% (10/29) of the patients. The median progression-free survival of patients with irAEs was significantly greater than that of patients without irAEs (5.8 months vs. 1.2 months, respectively; P = 0.028). The neutrophil to lymphocyte ratio (NLR) after 4 weeks of treatment in the complete response (CR) or partial response (PR) group was significantly lower than that in the stable disease (SD) or progression disease (PD) group (2.2 vs. 2.9, respectively; P = 0.044). The prognostic nutrition index (PNI) before treatment in the CR or PR group was significantly higher than that in the SD or PD group (37.1 vs. 32.1, respectively; P = 0.011). The PNI 8 weeks after treatment and the Glasgow prognostic score (GPS) before treatment were significantly associated with a poor outcome. Conclusion  The irAE, NLR, PNI, and GPS may be useful predictive markers for nivolumab efficacy in patients with advanced gastric cancer. Keywords  Gastric cancer · Programmed death-1 · Immune checkpoint inhibitor · Immune-related adverse events · Neutrophil to lymphocyte ratio · Prognostic nutrition index

Introduction Gastric cancer is the fifth most common cancer and the third-leading cause of cancer-related mortality worldwide [1]. The treatment of unresectable advanced or metastatic gastric cancer involves systemic therapy with cytotoxic chemotherapy or molecular targeting agents [2]. Programmed death 1 (PD-1) protein is a T-cell coinhibitory receptor with a structure similar to that of cytotoxic T-lymphocyte-associated antigen 4, but with a distinct biologic * Tsutomu Namikawa tsutomun@kochi‑u.ac.jp 1



Department of Surgery, Kochi Medical School, Kohasu, Oko‑cho, Nankoku, Kochi 783‑8505, Japan



Department of Human Health and Medical Sciences, Kochi Medical School, Kochi, Japan

2

function and ligand specificity [3]. Recently, immunotherapy with immune checkpoint inhibitors (ICIs) has contributed greatly to the development of treatment strategies for several malignanc