The prognostic impact of various circulating cytokine levels on response to EGFR-TKIs treatment in advanced NSCLC patients

Background: Non-small-cell lung cancer (NSCLC) patients were routinely treated with EGFR tyrosine kinase inhibitors (TKIs) and eventually acquired resistance from TME-producing intermediate factors, including various cytokines to facilitate cancer progression.Objective: To evaluate the correlation between circulating levels of pro-and anti-inflammatory cytokines and clinical outcomes in advanced NSCLC patients with EGFR mutant-receiving TKI treatments.Methods: Plasma samples were collected at pretreatment and during the 6-to 12-week follow-up in 123 patients with EGFR-mutated NSCLC.The expression of human cytokines was measured using a 27-bioplex panel by comparing the results to healthy controls (N=30).Patients were classified as durable responders (DU) based on progression-free survival (PFS): PFS ~* 104 weeks, and non-durable responders (NDU): PFS < 104 weeks.Results: High IL-6 and IL-10 levels at baseline were significant in NDU (P = 0.0076 and P = 0.0166, respectively).Low IL-6 levels were statistically significant in NDU (median difference = -1.275pg/ml, P = 0.0019) at the second time point.In contrast, IL-10 levels post-treatment were higher than baseline in DU [median difference = 0.000 pg/ ml, P = 0.0234].High IL-6 levels at pre-treatment were associated with poor PFS [(44.429 vs. 140.857),P = 0.018], overall-survival (OS) [(87 vs. 160), P < 0.001] and time-to-treatment failure (TTF) [(47 vs. 136), P < 0.001].In contrast, high IL-10 levels were associated with longer TTF (124.895 vs. 41.14 0 , P < 0.005). Conclusion:The pattern and levels of pro-and anti-inflammatory cytokines may be a prognostic biomarker for evaluating durable response in EGFR-mutant NSCLC patients who received targeted therapy.