Elsevier

Lung Cancer

Volume 152, February 2021, Pages 27-33
Lung Cancer

Clinical utility of pretreatment Glasgow prognostic score in non-small-cell lung cancer patients treated with immune checkpoint inhibitors

https://doi.org/10.1016/j.lungcan.2020.11.026Get rights and content

Highlights

  • GPS is calculated based on serum albumin and C-reactive protein values.

  • GPS was associated with DCR in NSCLC patients treated with ICI.

  • GPS was an independent prognostic factor in NSCLC patients receiving ICI.

  • GPS was the most powerful prognostic factor of the GPS, mGPS, and CAR.

Abstract

Objectives

Immune checkpoint inhibitors (ICIs) have become one of the standard therapies in non-small-cell lung cancer (NSCLC). Although inflammatory indices, including Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and C-reactive protein/albumin ratio (CAR) were reported to be reliable predictors for survival in cancer patients, their clinical utility in NSCLC patients treated with ICIs is unknown.

Materials and methods

Advanced or recurrent NSCLC patients (n = 304) treated with ICI monotherapy at the National Hospital Organization Kyushu Cancer Center and Kyushu University Hospital between January 2016 and December 2019 were analyzed. Information on patient demographics, GPS, mGPS, and CAR at diagnosis were collected. The time-dependent area under curves (AUCs) of receiver operating characteristic curves for the prediction of overall survival (OS) for each factor were compared.

Results

Of the three indices, GPS was the most significantly correlated with the degree of disease control rate (DCR) (DCR of GPS of 0, 1, and 2: 63.6 %, 49.4 %, and 41.4 %, respectively). The time-dependent AUC values of GPS for the prediction of OS were superior to those of mGPS and CAR (time-dependent AUC values of GPS, mGPS, and CAR for the prediction of 1-year OS: 0.7005, 0.6736, and 0.6565, respectively). GPS was significantly correlated with performance status (PS) (P <  0.0001) and clinical stage (P =  0.0139). GPS in combination with PS effectively predicted survival at 1 year ranging from 83.5 % (GPS = 0, PS = 0) to 25.0 % (GPS = 2, PS = 2, 3). A multivariable analysis revealed that GPS was an independent predictor of PFS and OS (P =  0.0009 and P =  0.0100, respectively).

Conclusions

We report for the first time that GPS represents a simple and useful prognostic factor in NSCLC patients treated with ICIs and should be validated prospectively.

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.

References (39)

  • H. Borghaei et al.

    Nivolumab versus Docetaxel in advanced nonsquamous non-small-Cell lung Cancer

    N. Engl. J. Med.

    (2015)
  • J. Brahmer et al.

    Nivolumab versus Docetaxel in advanced squamous-cell non-small-Cell lung Cancer

    N. Engl. J. Med.

    (2015)
  • M. Reck et al.

    Pembrolizumab versus chemotherapy for PD-L1-Positive non-small-Cell lung Cancer

    N. Engl. J. Med.

    (2016)
  • A.G. Sacher et al.

    Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-Cell lung Cancer: a review

    JAMA Oncol.

    (2016)
  • D.R. Gandara et al.

    Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab

    Nat. Med.

    (2018)
  • S. Takamori et al.

    Predictive and prognostic impact of primary tumor-bearing lobe in nonsmall cell lung cancer patients treated with anti-PD-1 therapy

    Int. J. Cancer

    (2020)
  • K. Takada et al.

    Clinical impact of skeletal muscle area in patients with non-small cell lung cancer treated with anti-PD-1 inhibitors

    J. Cancer Res. Clin. Oncol.

    (2020)
  • D.J. Pinato et al.

    Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer

    Br. J. Cancer

    (2014)
  • S. Takamori et al.

    The C-Reactive Protein/Albumin ratio is a novel significant prognostic factor in patients with malignant pleural mesothelioma: a retrospective multi-institutional study

    Ann. Surg. Oncol.

    (2018)
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