Identification of biomarkers associated with enhanced survival in lung cancer patients undergoing immune checkpoint inhibitor treatment.

INTRODUCTION Immunotherapy has revolutionized lung cancer treatment but has a relatively low response rate. Identification of predictive biomarkers could potentially identify patients for whom response can be expected. In this study, we aim to identify biomarkers from routine lab samples associated with better progression-free survival (PFS) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC), receiving immune checkpoint inhibitors (ICIs).

Methods

Patients aged ≥18 with advanced stage (III and IV) lung cancer, treated with ICIs and who signed the OncoLifeS data-biobank informed consent were included. We conducted univariate and multivariable Cox-regression analyses to identify blood-based biomarkers associated with PFS and OS (adjusted for PD-L1 expression, ECOG performance status, cancer stage, treatment line, type of treatment, histological type, age, body mass index, smoking status and sex).

Results

In total, 411 patients were included. Median PFS was 4.8 (interquartile range [IQR]: 1.49-16.67) months, and the median OS was 11.0 (IQR: 4.44-24.61) months. After Holm-Bonferroni correction, multivariable Cox-regression identified a decrease of neutrophil lymphocyte ratio (NLR), neutrophil count, lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), c-reactive protein (CRP) and an increase in albumin to be significantly associated with lowered risk of progression and death. A decrease in cortisol and increase in creatinine was significantly associated with improved survival, but not PFS.

Conclusion

These findings suggest that biomarkers reflecting reduced inflammation, absence of metastasis and potentially improved nutritional status may be associated with improved PFS and OS in patients with advanced NSCLC receiving ICIs.