Progastrin-Releasing Peptide Precursor and Neuron-Specific Enolase Predict the Efficacy of First-Line Treatment with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors Among Non-Small-Cell Lung Cancer Patients Harboring EGFR Mutations.

Purpose: Lung cancer is the leading cause of cancer-related mortality and non-small-cell lung cancer (NSCLC) accounts for 80-90% of all lung cancers. However, biomarkers to predict the prognosis of NSCLC patients upon treatment with tyrosine kinase inhibitors remain unreliable. Different types of EGFR mutations can help predict the efficacy of tyrosine kinase inhibitor (TKI) treatment among advanced NSCLC patients harboring them. However, survival varies among individuals harboring the same mutation after targeted therapy. This study aimed to investigate the value of serum tumor markers (STMs) and EGFR mutations in the prognostic assessment of progression-free survival (PFS) in advanced-stage EGFR-mutated NSCLC. Patients and Methods: A retrospective clinical review was performed on 81 NSCLC patients harboring EGFR mutations and for whom STM data, measured before commencement of first-line treatment with tyrosine kinase inhibitors, were available. Associations among EGFR mutations, STMs, baseline clinical features, and PFS were analyzed. Kaplan -Meier method was used to plot survival curves, and Cox logistic regression models were used to identify independent prognostic factors. Results: Exon 19 deletion (19-del) in EGFR, negative neuron-specific enolase (NSE), negative pro-gastrin-releasing peptide precursor (ProGRP) value, and "never smoking" status were significantly associated with improved PFS (P=0.007, P=0.001, P<0.001, and P<0.001, respectively). Multivariate Cox analysis revealed that 19-del in EGFR, never smoking, negative ProGRP value, and negative NSE were independent predictors of PFS. Conclusion: This study demonstrated that 19-del in EGFR may predict longer PFS in advanced-stage EGFR-mutated NSCLC treated with TKIs. Additionally, longer PFS can be predicted by serum tumor markers with negative ProGRP value, negative NSE value before initial treatment, and "never smoking." Therefore, in addition to the EGFR mutation type and smoking status, physicians can also prognosticate the PFS of tyrosine kinase inhibitors treatment according to the values of ProGRP and NSE before treatment.