ABSTRACT
Aim: Non-small cell lung cancer (NSCLC) is a commonly occurring and potentially fatal type of cancer. The aim of this study is to investigate the effects of clinical, laboratory, and systemic inflammatory response data on progression-free survival (PFS) and overall survival (OS) in metastatic NSCLC patients who were treated with nivolumab as a second-line treatment following platinum-based therapy. Materials and Methods: The sample of this retrospective single-center study consisted of 84 adult patients with metastatic NSCLC receiving nivolumab as second-line treatment. Demographic data, cancer diagnosis-related characteristics and laboratory parameters of the patients just before nivolumab was started were recorded. The C-reactive protein/albumin ratio (CAR), aspartate aminotransferase/alanine aminotransferase (De Ritis) ratio, Glasgow prognostic score (GPS), neutrophil/ lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) parameters were calculated for each patient. Results: The mean age for all participants was 62.08 ± 8.43 years. The median PFS and OS were 6.4 and 13 months, respectively. In the univariate risk analysis for PFS, Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p=0.05), and CAR (p=0.046) were identified as significant prognostic risk factors for PFS. However, the multivariate analysis did not confirm these two parameters as prognostic factors for PFS. In the multivariate analysis, ECOG PS (HR=0.45, 95% CI 0.22–0.94, p=0.035), bone metastasis (HR=0.38, 95% CI 0.19–0.78, p=0.008), and the De Ritis ratio (HR=0.47, 95% CI 0.23–0.96, p=0.037) remained independent prognostic risk factors of OS. Conclusion: In this study, in patients with metastatic NSCLC receiving nivolumab as second-line treatment, poor ECOG performance status, bone metastasis, and a high De Ritis ratio were identified as independent prognostic factors associated with shorter overall survival OS. These factors may help in evaluating patients' prognosis in clinical practice. Keywords: Lung cancer, nivolumab, prognostic factors, CAR, Deritis ratio
Cite this Article As :
Kapagan T, Bulut N, Erdem GU. Prognostic Risk Factors Affecting Survival in Patients With Metastatic Non-Small Cell Lung Cancer
Receiving Nivolumab As Second-Line Therapy. Selcuk Med J 2025;41(1): 29-35
1. Siegel RL, Miller KD and Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7-34. 20190108. DOI: 10.3322/caac.21551.
2. Institute NC. The Surveillance, Epidemiology, and End Results (SEER) Program, https://seer.cancer.gov/statfacts/html/lungb.html (2017, accessed 08.09.2023).
3. Nooreldeen R and Bach H. Current and Future Development in Lung Cancer Diagnosis. Int J Mol Sci 2021; 22 20210812. DOI: 10.3390/ijms22168661.
4. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143: e211S-e250S. DOI: 10.1378/chest.12-2355.
5. Lahiri A, Maji A, Potdar PD, et al. Lung cancer immunotherapy: progress, pitfalls, and promises. Mol Cancer 2023; 22: 40. 20230221. DOI: 10.1186/s12943-023-01740-y.
6. Kamada T, Togashi Y, Tay C, et al. PD-1(+) regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci U S A 2019; 116: 9999-10008. 20190426. DOI: 10.1073/pnas.1822001116.
7. Rendon A and Rayi A. Nivolumab. StatPearls. Treasure Island (FL), 2023.
8. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373: 123-135. 20150531. DOI: 10.1056/NEJMoa1504627.
9. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373: 1627-1639. 20150927. DOI: 10.1056/NEJMoa1507643.
10. Horn L, Spigel DR, Vokes EE, et al. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057). J Clin Oncol 2017; 35: 3924-3933. 20171012. DOI: 10.1200/JCO.2017.74.3062.
11. Bernichon E, Tissot C, Bayle-Bleuez S, et al. Predictive resistance factors in lung cancer patients treated with Nivolumab. Retrospective study. Bull Cancer 2021; 108: 250-265. 20201224. DOI: 10.1016/j.bulcan.2020.10.010.
12. Sabatier R, Nicolas E, Paciencia M, et al. Nivolumab in routine practice for older patients with advanced or metastatic non-small cell lung cancer. J Geriatr Oncol 2018; 9: 494-500. 20180309. DOI: 10.1016/j.jgo.2018.02.011.
13. Muchnik E, Loh KP, Strawderman M, et al. Immune Checkpoint Inhibitors in Real-World Treatment of Older Adults with Non-Small Cell Lung Cancer. J Am Geriatr Soc 2019; 67: 905-912. 20190130. DOI: 10.1111/jgs.15750.
14. Dall'Olio FG, Maggio I, Massucci M, et al. ECOG performance status >/=2 as a prognostic factor in patients with advanced non small cell lung cancer treated with immune checkpoint inhibitors-A systematic review and meta-analysis of real world data. Lung Cancer 2020; 145: 95-104. 20200506. DOI: 10.1016/j.lungcan.2020.04.027.
15. Yang K, Li J, Bai C, et al. Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis. Front Oncol 2020; 10: 1098. 20200709. DOI: 10.3389/fonc.2020.01098.
16. Schmid S, Diem S, Li Q, et al. Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC). Cancer Immunol Immunother 2018; 67: 1825-1832. 20180831. DOI: 10.1007/s00262-018-2239-4.
17. Song M, Zhang Q, Song C, et al. The advanced lung cancer inflammation index is the optimal inflammatory biomarker of overall survival in patients with lung cancer. J Cachexia Sarcopenia Muscle 2022; 13: 2504-2514. 20220714. DOI: 10.1002/jcsm.13032.
18. Mandaliya H, Jones M, Oldmeadow C, et al. II. Prognostic biomarkers in stage IV non-small cell lung cancer (NSCLC): neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) and advanced lung cancer inflammation index (ALI). Transl Lung Cancer Res 2019; 8: 886-894. DOI: 10.21037/tlcr.2019.11.16.
19. Arakawa Y, Miyazaki K, Yoshikawa M, et al. Value of the CRP-albumin ratio in patients with resectable pancreatic cancer. J Med Invest 2021; 68: 244-255. DOI: 10.2152/jmi.68.244.
20. Bezan A, Mrsic E, Krieger D, et al. The Preoperative AST/ALT (De Ritis) Ratio Represents a Poor Prognostic Factor in a Cohort of Patients with Nonmetastatic Renal Cell Carcinoma. J Urol 2015; 194: 30-35. 20150123. DOI: 10.1016/j.juro.2015.01.083.
21. Zhang F, Ying L, Jin J, et al. The C-reactive protein/albumin ratio predicts long-term outcomes of patients with operable non-small cell lung cancer. Oncotarget 2017; 8: 8835-8842. DOI: 10.18632/oncotarget.13053.
22. Kobayashi S, Karube Y, Matsumura Y, et al. Inflammatory Risk Factors for Early Recurrence of Non-Small Cell Lung Cancer Within One Year Following Curative Resection. World J Surg 2020; 44: 3510-3521. DOI: 10.1007/s00268-020-05612-0.
23. Miyazaki T, Saji H, Nakamura H, et al. The C-reactive protein to albumin ratio is a prognostic factor for stage I non-small cell lung cancer in elderly patients: JACS1303. Surg Today 2022; 52: 1463-1471. 20220224. DOI: 10.1007/s00595-022-02485-9.
24. Karahan I and Yalcin S. Is C-Reactive Protein/Albumin Ratio of Advanced-Stage Non-small Cell Lung Cancer Patients Able to Predict Mortality in the Admission for Palliative Care? Indian J Palliat Care 2020; 26: 365-368. 20200829. DOI: 10.4103/IJPC.IJPC_218_19.
25. Frey A, Martin D, D'Cruz L, et al. C-Reactive Protein to Albumin Ratio as Prognostic Marker in Locally Advanced Non-Small Cell Lung Cancer Treated with Chemoradiotherapy. Biomedicines 2022; 10 20220303. DOI: 10.3390/biomedicines10030598.
26. Ni XF, Wu J, Ji M, et al. Effect of C-reactive protein/albumin ratio on prognosis in advanced non-small-cell lung cancer. Asia Pac J Clin Oncol 2018; 14: 402-409. 20180904. DOI: 10.1111/ajco.13055.