Dynamics of Early Serum Tumour Markers and Neutrophil-to-Lymphocyte Ratio Predict Response to PD-1/PD-L1 Inhibitors in Advanced Non-Small-Cell Lung Cancer

Abstract

Yin Tang,1,2,* Yu Cui,3– 5,* Lin-lin Li,6,* Ya-ping Guan,3– 5 Dong-feng Feng,3– 5 Bei-bei Yin,3– 5 Xue-feng Liang,2 Jing Yin,2 Rui Jiang,6 Jing Liang,3– 5 Ya-hong Sun,2 Jun Wang3– 5 1Postgraduate Department, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 2Department of Oncology, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, 250031, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China; 4Shandong Lung Cancer Institute, Jinan, 250014, People’s Republic of China; 5Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, 250014, People’s Republic of China; 6Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ya-hong SunDepartment of Oncology, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), No. 38, Wu Yingshan Road, Tianqiao District, Jinan, 250031, People’s Republic of ChinaTel [phone]Email [email protected] WangDepartment of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Lixia District, Jinan, 250014, People’s Republic of ChinaTel [phone]Email [email protected]: To evaluate the dynamics of early serum tumour markers (STMs) and the neutrophil-to-lymphocyte ratio (NLR) to predict clinical efficacy and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who received programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors.Patients and Methods: We retrospectively reviewed patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors between September 2017 and August 2020. NLR and STMs were routinely measured between immunotherapy initiation and the first radiological evaluation. A combination score based on the leading STM and NLR and their dynamic changes was established. The effects of leading STM change, NLR change, and the combination score on the objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analysed. The accuracy of the combination score was evaluated by receiver operating characteristic (ROC) curve and the area under the curve (AUC).Results: Overall, 124 patients were included in this retrospective cohort study. The ORR was 22.8%, DCB was 54.5%, and the median OS and PFS were 21.6 and 14.9 months, respectively. Patients with low combination scores had a significantly improved ORR and DCB compared with those with intermediate or high scores (P = 0.002 for ORR, P < 0.0001 for DCB). In a multivariate model, the combination score was an independent indicator of PFS (P < 0.0001) and OS (P < 0.0001). The AUC demonstrated that the combination score (AUC = 0.706) has greater predictive power than either the posttreatment NLR (AUC = 0.668) or the leading STM change (AUC = 0.648) alone.Conclusion: An easy, cost-effective, and novel combination score based on the dynamics of an early STM and the NLR can accurately predict the clinical efficacy of PD-1/PD-L1 inhibitors and prognosis in advanced NSCLC patients.Keywords: serum tumour marker, neutrophil-to-lymphocyte ratio, PD-1 inhibitors, non-small-cell lung cancer, prognosis

Keywords

• serum tumour marker
• neutrophil-to-lymphocyte ratio
• pd-1 inhibitors
• non-small-cell lung cancer
• prognosis