Clinical utility of pretreatment Glasgow prognostic score in non-small-cell lung cancer patients treated with immune checkpoint inhibitors
Introduction
Lung cancer is one of the most fatal malignancies worldwide [1]. Non-small-cell lung cancer (NSCLC) accounts for 85 % of all lung cancers [2]. Recently, immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed death-ligand 1 (PD-L1) have received attention as novel immunotherapies for NSCLC patients [[3], [4], [5]]. Previous studies have shown that PD-L1 expression on tumor cells is a promising predictor of response in NSCLC patients treated with anti-PD-L1 therapy [6,7]. However, these predictors are not definitive and additional biomarkers for predicting response to ICIs are currently being investigated [[8], [9], [10], [11]].
Inflammatory indices, including the Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein (CRP)/albumin ratio (CAR), have been shown to be significant indicators of poor prognosis in cancer patients [[12], [13], [14]]. In patients with operable and inoperable NSCLC, GPS and mGPS were demonstrated to be reliable prognostic factors [15]. In patients with malignant pleural mesothelioma, CAR was an independent prognostic index [13]. However, it remains to be determined whether these inflammatory indices predict the efficacy of ICIs in NSCLC patients. Therefore, in the current retrospective study, we investigated the relationship between inflammatory indices and treatment outcome in NSCLC patients treated with ICIs. In addition, we analyzed which of these prognostic factors (GPS, mGPS, or CAR) was the most significant in this patient population.
Section snippets
Patients
We retrospectively identified 304 patients with advanced or recurrent NSCLC who were treated with ICI monotherapy (nivolumab, pembrolizumab, or atezolizumab) between January 2016 and December 2019 at the National Hospital Organization Kyushu Cancer Center (n = 179) and Kyushu University Hospital (n = 125). The patients received nivolumab, pembrolizumab, and atezolizumab intravenously at a dose of 3 mg/kg every 2 weeks, at a fixed dose of 200 mg every 3 weeks, and at a fixed dose of 1200 mg
Patient characteristics
The patient characteristics are shown in Table 1. Three hundred and four patients were included in the study. The median age was 66 years old. Most patients were male (79.6 %) with an ECOG PS of 0 or 1 (92.1 %). Most patients received ICI as second line therapy or higher (81.6 %), were ever-smokers (83.2 %), and had stage IIIB or IV disease (83.2 %). Driver oncogene (EGFR) mutational status data was available for 276 (90.8 %) patients, whereas PD-L1 tumor expression data was available for 211
Discussion
In this retrospective study, we demonstrated that pretreatment GPS was the most robust prognostic factor compared with mGPS and CAR in NSCLC patients treated with ICIs. This is the first report describing the clinical utility of GPS as a prognostic factor in cancer patients treated with ICIs. GPS can be described simply as albumin concentration less than 3.5 g/dl and a CRP level greater than 1.0 mg/dl, and each are given a score of 1. GPS is a useful prognostic factor in NSCLC patients
Data accessibility
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Ethical approval
This study was approved by our institutional review boards (National Hospital Organization Kyushu Cancer Center, IRB No. 2019-45 and Kyushu University, IRB No. 2019-195).
Funding
There are no sources of funding to report.
CRediT authorship contribution statement
Shinkichi Takamori: Conceptualization, Methodology, Writing - original draft. Kazuki Takada: Investigation, Writing - review & editing. Mototsugu Shimokawa: Methodology, Formal analysis. Taichi Matsubara: Data curation, Writing - review & editing. Takatoshi Fujishita: Data curation, Resources. Kensaku Ito: Data curation, Writing - review & editing, Resources. Ryo Toyozawa: Data curation, Writing - review & editing. Masafumi Yamaguchi: Data curation, Writing - review & editing. Tatsuro Okamoto:
Declaration of Competing Interest
As a potential personal and financial conflict of interest, Mototsugu Shimokawa reports personal fees from Sysmex. Ryo Toyozawa reports personal fees from Kyowa Hakko Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., and grants from Abbvie, Daiichi Sankyo Co. Ltd., Pfizer Japan, Takeda Pharmaceutical Co. Ltd. Masafumi Yamaguchi reports personal fees from AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd, Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co., Ltd., and grants
Acknowledgments
We thank Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript. The publication fee was funded by Japanese Foundation for Multidisciplinary Treatment of Cancer.
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