Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study

Overview

Journal Target Oncol

Specialty Oncology

Date 2024 Jul 11

PMID 38990462

Authors

Kinnosuke Matsumoto

Yuji Yamamoto

Takayuki Shiroyama

Tomoki Kuge

Masahide Mori

Motohiro Tamiya

Yuhei Kinehara

Akihiro Tamiya

Hidekazu Suzuki

Satoshi Tobita

Kiyonobu Ueno

Toshie Niki

Izumi Nagatomo

Yoshito Takeda

Atsushi Kumanogoh

Affiliations

Soon will be listed here.

Abstract

Background: Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce.

Objective: We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy.

Methods: This multicenter, real-world cohort study included chemonaive patients who underwent chemoimmunotherapy between December 2018 and May 2022. Multivariate analysis was used to determine associations between survival outcomes and patient background, including baseline neutrophil-to-lymphocyte ratio (NLR) and its dynamic change (ΔNLR). To further investigate the clinical significance of NLR, patients were classified based on their peripheral immune status, defined by a combination of NLR and ΔNLR.

Results: The study included 280 patients with 30.1 months of median follow-up. Multivariate analysis revealed that older individuals, poor performance status, tumor proportion score < 1%, liver metastasis, baseline NLR ≥ 5, and ΔNLR ≥ 0 independently correlated significantly with shorter progression-free and overall survival (OS). Patients with high peripheral immune status (defined as NLR <5 and ΔNLR < 0) significantly improved long-term survival (2-year OS rate of 58.3%), whereas those with low peripheral immune status (defined as NLR ≥ 5 and ΔNLR ≥ 0) had extremely poor outcomes (2-year OS rate of 5.6%). Safety profiles did not differ significantly in terms of severe adverse events and treatment-related death rates despite the patients' peripheral immune status (P = 0.46 and 0.63, respectively).

Conclusions: Our study provides real-world evidence regarding clinical prognostic factors for the efficacy of chemoimmunotherapy. The combined assessment of baseline NLR and ΔNLR could facilitate the identification of patients who are likely to achieve a durable response from chemoimmunotherapy.

References

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J . Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379(21):2040-2051. DOI: 10.1056/NEJMoa1810865. View

Restifo N, Dudley M, Rosenberg S . Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012; 12(4):269-81. PMC: 6292222. DOI: 10.1038/nri3191. View

Ricciuti B, Dahlberg S, Adeni A, Sholl L, Nishino M, Awad M . Immune Checkpoint Inhibitor Outcomes for Patients With Non-Small-Cell Lung Cancer Receiving Baseline Corticosteroids for Palliative Versus Nonpalliative Indications. J Clin Oncol. 2019; 37(22):1927-1934. DOI: 10.1200/JCO.19.00189. View

Brueckl W, Ficker J, Zeitler G . Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC). BMC Cancer. 2020; 20(1):1185. PMC: 7713034. DOI: 10.1186/s12885-020-07690-8. View

Arbour K, Mezquita L, Long N, Rizvi H, Auclin E, Ni A . Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. J Clin Oncol. 2018; 36(28):2872-2878. DOI: 10.1200/JCO.2018.79.0006. View

Chen S, Li R, Zhang Z, Huang Z, Cui P, Jia W . Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors. Transl Lung Cancer Res. 2021; 10(3):1397-1407. PMC: 8044483. DOI: 10.21037/tlcr-21-43. View

Petrelli F, Signorelli D, Ghidini M, Ghidini A, Pizzutilo E, Ruggieri L . Association of Steroids use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Cancers (Basel). 2020; 12(3). PMC: 7139305. DOI: 10.3390/cancers12030546. View

Kawachi H, Yamada T, Tamiya M, Negi Y, Goto Y, Nakao A . Concomitant Proton Pump Inhibitor Use With Pembrolizumab Monotherapy vs Immune Checkpoint Inhibitor Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer. JAMA Netw Open. 2023; 6(7):e2322915. PMC: 10336622. DOI: 10.1001/jamanetworkopen.2023.22915. View

Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F . Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 378(22):2078-2092. DOI: 10.1056/NEJMoa1801005. View

10.

Kunimasa K, Matsumoto S, Kawamura T, Inoue T, Tamiya M, Kanzaki R . Clinical application of the AMOY 9-in-1 panel to lung cancer patients. Lung Cancer. 2023; 179:107190. DOI: 10.1016/j.lungcan.2023.107190. View

11.

Liu D, Jin J, Zhang L, Li L, Song J, Li W . The Neutrophil to Lymphocyte Ratio May Predict Benefit from Chemotherapy in Lung Cancer. Cell Physiol Biochem. 2018; 46(4):1595-1605. DOI: 10.1159/000489207. View

12.

Chen Q, Zhang Z, Li X, Feng S, Liu S . Analysis of prognostic factors affecting immune checkpoint inhibitor therapy in tumor patients exposed to antibiotics. Front Oncol. 2023; 13:1204248. PMC: 10358726. DOI: 10.3389/fonc.2023.1204248. View

13.

Socinski M, Jotte R, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N . Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018; 378(24):2288-2301. DOI: 10.1056/NEJMoa1716948. View

14.

Sordo-Bahamonde C, Lorenzo-Herrero S, Gonzalez-Rodriguez A, Martinez-Perez A, Rodrigo J, Garcia-Pedrero J . Chemo-Immunotherapy: A New Trend in Cancer Treatment. Cancers (Basel). 2023; 15(11). PMC: 10252089. DOI: 10.3390/cancers15112912. View

15.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

16.

Zhang W, Tan Y, Li Y, Liu J . Neutrophil to Lymphocyte ratio as a predictor for immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Front Immunol. 2023; 14:1234142. PMC: 10445236. DOI: 10.3389/fimmu.2023.1234142. View

17.

Banna G, Cantale O, Muthuramalingam S, Cave J, Comins C, Cortellini A . Efficacy outcomes and prognostic factors from real-world patients with advanced non-small-cell lung cancer treated with first-line chemoimmunotherapy: The Spinnaker retrospective study. Int Immunopharmacol. 2022; 110:108985. DOI: 10.1016/j.intimp.2022.108985. View

18.

Paz-Ares L, Ciuleanu T, Cobo M, Schenker M, Zurawski B, Menezes J . First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(2):198-211. DOI: 10.1016/S1470-2045(20)30641-0. View

19.

Grenader T, Nash S, Plotkin Y, Furuse J, Mizuno N, Okusaka T . Derived neutrophil lymphocyte ratio may predict benefit from cisplatin in the advanced biliary cancer: the ABC-02 and BT-22 studies. Ann Oncol. 2015; 26(9):1910-1916. DOI: 10.1093/annonc/mdv253. View

20.

Xia H, Zhang W, Zhang Y, Shang X, Liu Y, Wang X . Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis. Front Oncol. 2022; 12:978069. PMC: 9623244. DOI: 10.3389/fonc.2022.978069. View