Predictive value of clinical parameters in responses to epidermal growth factor-tyrosine kinase inhibitors as first-line therapy for stage Ⅳ non-small cell lung cancer

Abstract

Objective To analyze the relationship between the clinical parameters and the efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors (EGFR-TKIs) as the first-line therapy in patients with stage Ⅳ non-small cell lung cancer (NSCLC) and identify the clinical markers for predicting the patients' responses to the treatment. Methods The clinical data were retrospectively reviewed for the patients with stage Ⅳ EGFR mutation-positive NSCLC receiving EGFR-TKIs (erlotinib, gefitinib, and icotinib) as the first-line therapy in our hospital between January, 2010 and December, 2016, and the relationship between the patients' clinical parameters and responses to the treatment were analyzed. Results A total of 123 patients (43 males and 80 females, aged ranging from 28 to 84 years) were included in this study. The objective response rate (ORR) of the overall patients was 47.97%, the disease control rate (DCR) was 100%, the median progression-free survival (mPFS) time was 11.0 months, and the median overall survival (OS) time was 22.7 months. Univariate analysis showed that the patients with low levels of neuronspecific enolase (NSE), carbohydrate antigen 125 (CA125) or Cyfra21-1 before the treatment had significantly prolonged mPFS time (NES: 14.2 vs 9.1 months, P < 0.001; CA125: 12.4 vs 9.5 months, P=0.024; Cyfra21-1: 12.3 vs 9.5 months, P=0.033); the mOS time was significantly prolonged in patients with ECOG performance status of 0~1 (24.0 vs 16.5 months, P=0.001) and low levels of NSE (27.7 vs 17.3 months, P < 0.001), CA125 (25.4 vs 20.2 months, P=0.002), Cyfra21-1 (25.7 vs 18.1 months, P=0.027) or CA15-3 (25.5 vs 18.7 months, P=0.009). Multivariate analysis suggested that CA125 and NSE were independent prognostic factors of PFS, and CA125, NSE, CA15-3, hepatic metastasis and performance status were independent prognostic factors of the OS time. Combined analysis of CA125, Cyfra21-1, CA15-3 and NSE showed that compared with those with elevation of a single factor, the patients with elevation of multiple factors had shorter mPFS time (9.3 vs 11.8 months, P=0.045) and also shorter mOS time (18.7 vs 27.4 months, P=0.001). Conclusion Low levels of CA125 or NSE before first-line EGFR-TKIs treatment are associated with longer PFS time of the patients with stage Ⅳ NSCLC, while performance status of 0~1 and low levels of NSE, CA125 or CA15-3 are associated with a longer OS time of the patients. The combination of CA125, Cyfra21-1, CA15-3 and NSE is expected to serve as a simple indicator for predicting the efficacy of firstreceptor-line EGFR-TKIs therapy in patients with stage Ⅳ NSCLC.

Keywords

• non-small cell lung cancer
• epidermal growth factorreceptor-tyrosine kinase inhibitors
• clinical parameter
• tumor biomarker
• prognosis