Baseline Serum Cholesterol Levels Predict the Response of Patients with Advanced Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitor-Based Treatment

Abstract

Jingtao Tong III,1,* Yifei Mao,2,* Ziru Yang,1 Quan Xu,1 Zhen Zheng,1 Hui Zhang,1 Jingjing Wang,1 Sandian Zhang,1 Weibo Rong,3 Lu Zheng III1 1Department of Radiation Oncology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, 315040, People’s Republic of China; 2Department of Emergency Medicine, Ninghai First Hospital, Ningbo, 315600, People’s Republic of China; 3Department of Pharmacy, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, 315040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu ZhengDepartment of Radiation Oncology, Ningbo Medical Treatment Center Li Huili Hospital, No. 57, Xing Ning Road, Yinzhou District, Ningbo, 315040, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Although predictive markers of immune checkpoint inhibitor (ICI)-based treatments have been extensively studied, with the exception of programmed death ligand 1 (PD-L1), most are not widely used in the clinic due to poor effects or defective practicability. The aim of this study was to identify those patients with high baseline serum cholesterol who benefit from ICI-based treatments.Patients and Methods: Patients with advanced non-small cell lung cancer (NSCLC) treated at Ningbo Medical Center, Li Huili Hospital between August 2017 and December 2019 were enrolled in this retrospective study. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to evaluate the efficacy of the ICI-based treatment. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier survival curves and compared using the log rank test. Univariate and multivariate analyses were conducted using the logistic regression analysis and Cox proportional hazards model. A receiver operating characteristic curve was created, and the area under the curve (AUC) was calculated to compare the predictive value of baseline serum cholesterol with PD-L1 expression for patient response to ICI-based treatment.Results: In our cohort of 169 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) of the treatment were significantly higher in patients with hypercholesterolemia (> 5.18 mmol/L) than in those with hypocholesterolemia (ORR: 33.67% vs 14.08%, P=0.004; DCR: 68.37% vs 42.25%, P=0.001). The median PFS was 7.9 months in the hypercholesterolemia group, significantly longer than in the hypocholesterolemia group (4.4 months, 95% CI: 4.620– 7.380, P< 0.001). The median OS in the two groups were 11 months and 8 months, with 95% CIs of 8.980– 10.420 (P< 0.001). The AUC for the baseline level of cholesterol was 0.706 (P< 0.001), while it was 0.643 (P=0.001) for PD-L1 expression.Conclusion: The baseline serum cholesterol level is predictive of a clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, and hence it is a promising prognostic indicator for ICI-based treatment of NSCLC.Keywords: non-small cell lung cancer, NSCLC, serum cholesterol, immune checkpoint inhibitors, ICIs, prognostic marker

Keywords

• non-small cell lung cancer
• nsclc
• serum cholesterol
• immune checkpoint inhibitors
• icis
• prognostic marker