Clinical Significance of Serum Biomarkers in Stage IV Non-Small-Cell Lung Cancer Treated with PD-1 Inhibitors: LIPI Score, NLR, dNLR, LMR, and PAB

BACKGROUND: To assess the prognostic value of pretreatment serum biomarkers in stage IV non-small-cell lung cancer (NSCLC) patients treated with PD-1 (programmed cell death protein 1) inhibitors and their value as a predictor of benefit. METHODS: We performed a retrospective study including patients with stage IV NSCLC who were treated with anti-PD-1 drugs in first or advanced lines of therapy in the Affiliated Tumor Hospital of Nantong University. Serum biomarkers such as NLR, dNLR, LMR, PAB, ALB, and LIPI scores were calculated and analyzed in detail. RESULTS: A total of 85 patients with stage IV NSCLC treated with PD-1 inhibitors in the first or advanced lines of therapy were included in this subject. According to the tumor response of PD-1-based treatment, ORR was 42.4% (36/85) and DCR was 68.2% (58/85). The median OS and PFS were 20.0 months and 7.0 months, respectively. The ROC curves showed that the serum biomarkers of NLR, dNLR, LDH, LMR, PAB, and ALB were significantly associated with overall survival and helped to determine the cut-off value. The multivariate Cox proportional hazard analyses for stage IV NSCLC patients treated with PD-1 inhibitors indicated that dNLR (P < 0.001) and ALB (P = 0.033) were independent prognostic indicators of PFS, while liver metastasis (P = 0.01), NLR (P = 0.01), dNLR (P = 0.001), and LMR (P = 0.006) were independent prognostic indicators of OS. Moreover, patients of the good LIPI group showed prolonged PFS and OS than those with intermediate/poor LIPI score (P < 0.001 and P = 0.006, respectively). CONCLUSIONS: Pretreatment dNLR is an independent prognostic indicator of both PFS and OS in stage IV NSCLC patients treated with PD-1 inhibitors. Pretreatment LIPI, combining dNLR > 3 and LDH>ULN, was correlated with worse outcome for stage IV NSCLC patients treated with ICI. High NLR, high dNLR, low LMR, and low ALB at baseline might be useful as an early predictive biomarker of benefit.