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      A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: a pooled analysis of 14 retrospective studies

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          ABSTRACT

          Objective: Nivolumab has been used for treating non-small cell lung cancer (NSCLC) worldwide. Whether neutrophil-lymphocyte ratio (NLR) can predict the prognosis of NSCLC treated with Nivolumab is still under debate. This meta-analysis was to assess the significance of NLR as a predictive factor in NSCLC patients receiving Nivolumab.

          Methods: Databases including PubMed, Embase, and the Cochrane library were searched to identify eligible studies evaluating the role of NLR in predicting prognosis of NSCLC treated with Nivolumab until March 2018 without language restrictions. The meta-analysis was performed using hazard ratio (HR) of progression free survival (PFS) and overall survival (OS) in NSCLC patients with various NLR.

          Results: A total of 14 retrospective studies consisting of 1225 NSCLC patients were included. The combined results showed that relatively higher baseline NLR was associated with poor PFS (HR = 1.44; 95% confidence interval (CI):1.18–1.77; p < 0.05) and OS (HR = 1.75; 95% CI: 1.33–2.30; p < 0.05) after treatment of Nivolumab. Subgroup analysis suggested that NLR ≥ 5 was more reliable for PFS (HR = 1.73; 95%CI: 1.14, 2.62; p < 0.05) and OS (HR = 1.76; 95%CI: 1.47, 2.10; p < 0.05). In addition, post-treatment NLR also had predictive roles for PFS (HR = 3.17; 95%CI: 1.48, 6.82; p < 0.05) and OS (HR = 2.26; 95%CI: 1.05, 4.86; p < 0.05).

          Conclusion: Our findings suggest that NLR can be used as a prognostic biomarker for NSCLC treating with Nivolumab, and the recommended cutoff value of NLR is 5.

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          M Parmar, V. Torri, L. Stewart (1998)
          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis

            Danielle Benedict Sacdalan, Josephine Lucero, Dennis Sacdalan (2018)
            Introduction Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients. Methods We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs) using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs) were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor. Results/discussion A high NLR resulted in worse overall survival (OS) (HR, 1.92; 95% CI, 1.29–2.87; p=0.001) and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38–2.01; p<0.00001) across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer). Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.83; 95% CI, 0.97–3.44; p=0.06). A high NLR also showed worse OS and PFS across all ICIs (ipilimumab, nivolumab, and unspecified or pooled pembrolizumab and nivolumab; OS: HR, 1.92; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.66; 95% CI, 1.38–2.01; p<0.00001). Subgroup analysis by type of ICI showed similar results. Conclusion A high NLR is associated with poorer outcomes across studies. This shows that NLR has the potential as a readily available prognostic indicator for patients receiving ICI based on available studies. Studies utilizing more stringent design may serve to better determine the utility of this tool.
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              Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma

              Aly-Khan Lalani, Wanling Xie, Dylan Martini … (2018)
              Background An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB. Methods We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA). Landmark analysis at 6 weeks was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Cox and logistic regression models allowed for adjustment of line of therapy, number of IMDC risk factors, histology and baseline NLR. Results Median follow up was 16.6 months (range: 0.7–67.8). Median duration on therapy was 5.1 months (<1–61.4). IMDC risk groups were: 18% favorable, 60% intermediate, 23% poor-risk. Forty-four percent were on first-line ICB and 56% on 2nd line or more. Median NLR was 3.9 (1.3–42.4) at baseline and 4.1 (1.1–96.4) at week 6. Patients with a higher baseline NLR showed a trend toward lower ORR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was a significantly stronger predictor of all three outcomes than baseline NLR. Relative NLR change by ≥25% from baseline to 6 weeks after ICB therapy was associated with reduced ORR and an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.004), whereas a decrease in NLR by ≥25% was associated with improved outcomes. Conclusions Early decline and NLR at 6 weeks are associated with significantly improved outcomes in mRCC patients treated with ICB. The prognostic value of the readily-available NLR warrants larger, prospective validation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncoimmunology
                Journal ID (iso-abbrev): Oncoimmunology
                Journal ID (publisher-id): KONI
                Journal ID (publisher-id): koni20
                Title: Oncoimmunology
                Publisher: Taylor & Francis
                ISSN (Print): 2162-4011
                ISSN (Electronic): 2162-402X
                Publication date Collection: 2018
                Publication date (Electronic): 20 August 2018
                Publication date PMC-release: 20 August 2018
                Volume: 7
                Issue: 11
                Electronic Location Identifier: e1507262
                Affiliations
                [a ]Department of Oncology, RenMin Hospital of WuHan University , WuHan, Hubei, China
                [b ]Department of Oncology, The Fifth Hospital of WuHan , WuHan, Hubei, China
                [c ]Department of Hematology, The Union Hospital, Tongji Medical College, HuaZhong University of Science and Technology , WuHan, Hubei, China
                [d ]Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology , Wuhan, Hubei, China
                Author notes
                CONTACT Dedong Cao caodedong123@ 123456whu.edu.cn Department of Oncology, RenMin Hospital of WuHan University , WuHan, Hubei 430000, China

                Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/koni.

                Article
                Publisher ID: 1507262
                DOI: 10.1080/2162402X.2018.1507262
                PMC ID: 6205035
                PubMed ID: 30377569
                SO-VID: fb0d4d70-baaa-4cdb-a756-e7df266c6c1b
                Copyright © © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                History
                Date received : 18 April 2018
                Date revision received : 26 July 2018
                Date accepted : 29 July 2018
                Page count
                Figures: 4, Tables: 3, References: 39, Pages: 9
                Funding
                None
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Immunology
                Keywords: neutrophil-to-lymphocyte ratio,nivolumab,immunotherapy,lung cancer,meta-analysis
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: neutrophil-to-lymphocyte ratio, nivolumab, immunotherapy, lung cancer, meta-analysis

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