Correlation of high density lipoprotein cholesterol with resistance of epidermal growth factor receptor-tyrosine kinase inhibitor in advanced non-small-cell lung cancer

Abstract

Objective To explore the relevance of high density lipoprotein cholesterol (HDL-C) level and resistance of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced non-small cell lung cancer (NSCLC). Methods In a total of 87 NSCLC patients harboring EGFR mutation treated with EGFR-TKI, the correlations of pre-treatment levels of soluble HDL-C between efficacy and resistance of EGFR-TKI were analyzed by Kaplan-Meier method and Cox proportional hazard model. Results Patients with normal HDL-C (≥0.94 mmol/L) had a better disease control rate (DCR) than those with low HDL-C (<0.94 mmol/L) [94.5 % (52/55) vs 65.7 % (21/32), P< 0.001]. The results of univariate analysis showed that patients with normal HDL-C had longer progress free survival (PFS) (HR = 0.27, 95 % CI 0.164-0.444, P< 0.001). The results of multivariate Cox proportional hazard model analysis with sex, pathologic histology, smoking history and mutation type showed that only HDL-C group had a significant difference (P< 0.001). The same results were showed when stratified by sex and smoking history (female: P< 0.001, male: P= 0.002; Smoker: P< 0.001, non-smoker: P= 0.014). Conclusion Normal pre-treatment serum levels of HDL-C are associated with a better outcome and longer progression-free survival in NSCLC patients treated with EGFR-TKI, which may be a predictive marker for a better response. Key words: Carcinoma, non-small-cell lung; High density lipoprotein cholesterol; Epidermal growth factor; Tyrosine kinase inhibitors; Molecular targeted therapy; Drug resistance, neoplasm