Neutrophil-to-lymphocyte ratio as a prognostic marker in highly PD-L1 expressing advanced non-small cell lung cancer patients in first line treatment with pembrolizumab
DOI:
https://doi.org/10.32932/gecp.2023.10.037Keywords:
Lung cancer, pembrolizumab, PD-L1, neutrophil-lymphocyte ratio, Non-small Cell Lung Cancer (NSCLC)Abstract
Introduction and objectives: The neutrophil-lymphocyte ratio (NLR) has been proposed to assess advanced stage non-small cell lung cancer (aNSCLC) response to immunotherapy, given the easy availability and low cost. The aim of our study was to evaluate the relationship between NLR at baseline, after the 3rd and 6th treatment cycles, and progression free survival (PFS) and overall survival (OS), in a population with aNSCLC with a PD-L1 expression ≥50% treated with pembrolizumab monotherapy in first line.Methods: We performed a retrospective study of patients with aNSCLC with PD-L1≥50% who were treated with pembrolizumab first line from February 2017 to July 2021. NLR values at baseline and after the 3rd and 6th pembrolizumab cycles were analyzed. Optimal NLR cut-off were determined with respect to OS, by ROC curve. PFS and OS were compared by Kaplan Meyer method and Cox Proportional Hazard model for NLR measures.
Results: Sixty-six patients with PD-L1≥50% (51% males, mean age 65.8 ± 11.2 years) were included in the study. The PD-L1 expression was ≥90% in 74% of the patients. NLR≤4 after the 3rd pembrolizumab cycle were associated with a significant improvement in PFS (23.6 vs 4.3 months, p=0.002) and OS (32.9 vs 6.3 months, p=0.022), compared with NLR>4.
Discussion and conclusions: In patients with aNSCLC and a PD-L1≥50% receiving frontline pembrolizumab treatment, low NLR values after the 3rd pembrolizumab cycle were associated with significantly longer PFS and OS. This biomarker may thus help identify individuals on pembrolizumab monotherapy who are at greatest risk for disease progression.
Downloads
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. https://doi.org/10.3322/caac.21660
Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol 2019;37:537-46. https://doi.org/10.1200/JCO.18.00149
Rafei H, El-Bahesh E, Finianos A, Nassereddine S, Tabbara I. Immune-based Therapies for Non-small Cell Lung Cancer. Anticancer Res 2017;37:377-87. https://doi.org/10.21873/anticanres.11330
Wherry EJ. T cell exhaustion. Nat Immunol 2011;12:492-9. https://doi.org/10.1038/ni.2035
Takada K, Toyokawa G, Shoji F, Okamoto T, Maehara Y. The Significance of the PD-L1 Expression in Non-Small-Cell Lung Cancer: Trenchant Double Swords as Predictive and Prognostic Markers. Clin Lung Cancer 2018;19:120-9. https://doi.org/10.1016/j.cllc.2017.10.014
Li M, Spakowicz D, Burkart J, Patel S, Husain M, He K, et al. Change in neutrophil to lymphocyte ratio during immunotherapy treatment is a non-linear predictor of patient outcomes in advanced cancers. J Cancer Res Clin Oncol 2019;145:2541-6. https://doi.org/10.1007/s00432-019-02982-4
Jiang T, Bai Y, Zhou F, Li W, Gao G, Su C, et al. Clinical value of neutrophil-to-lymphocyte ratio in patients with non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors. Lung Cancer 2019;130:76-83. https://doi.org/10.1016/j.lungcan.2019.02.009
Valero C, Pardo L, Lopez M, Garcia J, Camacho M, Quer M, et al. Pretreatment count of peripheral neutrophils, monocytes, and lymphocytes as independent prognostic factor in patients with head and neck cancer. Head Neck 2017;39:219-26. https://doi.org/10.1002/hed.24561
MacDougall K, Niazi MRK, Hosry J, Homsy S, Bershadskiy A. The Prognostic Significance of Peripheral Blood Biomarkers in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab: A Clinical Study. Oncology (Williston Park) 2022;36:156-61. https://doi.org/10.46883/25920954
Ksienski D, Wai ES, Alex D, Croteau NS, Freeman AT, Chan A, et al. Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab. Transl Lung Cancer Res 2021;10:355-67. https://doi.org/10.21037/tlcr-20-541
Takada K, Takamori S, Yoneshima Y, Tanaka K, Okamoto I, Shimokawa M, et al. Serum markers associated with treatment response and survival in non-small cell lung cancer patients treated with anti-PD-1 therapy. Lung Cancer 2020;145:18-26. https://doi.org/10.1016/j.lungcan.2020.04.034
Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol 2019;16:601-20. https://doi.org/10.1038/s41571019-0222-4
Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A. Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev Cancer 2020;20:485-503. https://doi.org/10.1038/s41568-020-0281-y
Faget J, Peters S, Quantin X, Meylan E, Bonnefoy N. Neutrophils in the era of immune checkpoint blockade. J Immunother Cancer 2021;9. https://doi.org/10.1136/jitc-2020-002242
Kacan T, Babacan NA, Seker M, Yucel B, Bahceci A, Eren AA, et al. Could the neutrophil to lymphocyte ratio be a poor prognostic factor for non small cell lung cancers? Asian Pac J Cancer Prev 2014;15:2089-94. https://doi.org/10.7314/apjcp.2014.15.5.2089
Kazandjian D, Gong Y, Keegan P, Pazdur R, Blumenthal GM. Prognostic Value of the Lung Immune Prognostic Index for Patients Treated for Metastatic Non-Small Cell Lung Cancer. JAMA Oncol 2019;5:1481-5. https://doi.org/10.1001/jamaoncol.2019.1747
Kubo S, Kobayashi N, Somekawa K, Hirata M, Kamimaki C, Aiko H, et al. Identification of Biomarkers for Non-small-cell Lung Cancer Patients Treated With an Immune Checkpoint Inhibitor. Anticancer Res 2020;40:3889-96. https://doi.org/10.21873/anticanres.14379
Egami S, Kawazoe H, Hashimoto H, Uozumi R, Arami T, Sakiyama N, et al. Peripheral blood biomarkers predict immune-related adverse events in non-small cell lung cancer patients treated with pembrolizumab: a multicenter retrospective study. J Cancer 2021;12:2105-12. https://doi.org/10.7150/jca.53242
Ayers KL, Ma M, Debussche G, Corrigan D, McCafferty J, Lee K, et al. A composite biomarker of neutrophil-lymphocyte ratio and hemoglobin level correlates with clinical response to PD-1 and PD-L1 inhibitors in advanced non-small cell lung cancers. BMC Cancer 2021;21:441. https://doi.org/10.1186/s12885-021-08194-9
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. https://doi.org/10.1016/j.ejca.2008.10.026
Beer L, Hochmair M, Prosch H. Pitfalls in the radiological response assessment of immunotherapy. Memo 2018;11:138-43. https://doi.org/10.1007/s12254-018-0389-x
Popat S, Liu SV, Scheuer N, Gupta A, Hsu GG, Ramagopalan SV, et al. Association Between Smoking History and Overall Survival in Patients Receiving Pembrolizumab for First-Line Treatment of Advanced Non-Small Cell Lung Cancer. JAMA Netw Open 2022;5:e2214046. https://doi.org/10.1001/jamanetworkopen.2022.14046
Dai L, Jin B, Liu T, Chen J, Li G, Dang J. The effect of smoking status on efficacy of immune checkpoint inhibitors in metastatic non-small cell lung cancer: A systematic review and meta-analysis. EClinicalMedicine 2021;38:100990. https://doi.org/10.1016/j.eclinm.2021.100990
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature 2013;500:415-21. https://doi.org/10.1038/nature12477
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Author(s) (or their employer(s)) and THORAC 2024
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
