P2.13-19 Prognostic Value Inferred from the Quantitative Measurement of EGFR Mutation Using PNA-Clamping Method in Advanced EGFR Mutant NSCLC Patients

Abstract

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Recent advances in the understanding of the biology of tumors and in highly sensitive detection technologies for molecular analysis offer targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, not all EGFR mutation positive NSCLC patients are equally responsive to EGFR-TKIs. Although many factors have been introduced to predict EGFR TKIs response, there seems to be no factor that can clearly explain the mechanism. The aim of this study was to evaluate whether the quantification of EGFR mutation predicts clinical outcomes of EGFR-TKI therapy. This study is retrospective analysis of prospectively collected data about all patients who underwent EGFR mutation test using peptide nucleic acid (PNA)-mediated clamping polymerase chain reaction (PCR) at the Pusan National University Hospital between October 2015 and December 2017. The efficiency of PCR clamping was determined by measuring the Ct value. The delta (Δ) Ct-1 value (standard Ct value minus sample Ct value) was calculated to measure the quantification of EGFR mutation. Among the total 552 patients tested for EGFR mutations and 142 (25.7%) were positive for EGFR mutations. Seventy-one patients received EGFR-TKIs. The patient population was subdivided using a mean ΔCt-1 value of 5.28. There was no clinically significant difference between the two groups. Patients with high ΔCt-1 value had significantly longer median overall survival (OS) than did patients with low ΔCt-1 value (24.5 vs 16.7 months, p=0.002). Patients with common EGFR mutation (exon 19 deletion or L858R) and high ΔCt-1 value showed a significantly longer median OS than did patients with common mutation and low ΔCt-1 value (24.1 vs 18.0 months, p=0.014). Multivariate analysis revealed only high ΔCt-1 value was significant prognostic factor of survival in advanced advanced EGFR mutant NSCLC. The ΔCt-1 value, which refers to EGFR quantification by PNA-clamping method, is a significant good prognostic factor of survival to EGFR-TKI therapy.