Abstract A31: Comparison of direct sequencing and peptide nucleic acid clamping of EGFR gene in patients with non-small cell lung cancer.

Abstract

Abstract Background: Direct sequencing is considered as a gold standard for the detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC), but low sensitivity is a problem. The aim of this study is to prove higher detection rate of EGFR mutation with peptide nucleic acid (PNA) clamping compared to direct sequencing. Methods: This is a single arm, open label, prospective, observational study for patients with stage IIIB, IV or relapsed NSCLC. A sample size of 140 pairs will have 90% power to detect a difference in proportions of 0.1 when the proportion of discordant pairs is expected to be 0.16 and the method of analysis is a McNemar's test of equality of paired proportions with a 0.05 one-sided significance level and 20% drop out rate. Tumor DNA samples were obtained from paraffin block or cytology specimen. Both direct sequencing and PNA clamping for EGFR gene in exon 18, 19, 20 and 21 were performed. Results: Of 138 paired test sets, 24 mutations of EGFR gene were detected by direct sequencing (17.4%) and 45 mutations were detected by PNA clamping (32.6%). The difference of detection rate between two methods was 15.2% (95% Confidence Interval: 8.7-17.8%, p<0.001). After treatment with EGFR-tyrosine kinase inhibitors, 20 of 26 response evaluable patients with EGFR mutation by PNA clamping showed partial responses (PR, 76.9%). And 8 among 13 patients with EGFR mutation by direct sequencing showed PR (61.5%). Conclusion: This study proved that PNA clamping has significantly higher detection rate of EGFR mutation compared with direct sequencing. (ClinicalTrials.gov number, NCT01767974) Citation Format: Young-Chul Kim, Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Bo-Ram Lee, Jin-Yeong Yu, Min-Ki Lee. Comparison of direct sequencing and peptide nucleic acid clamping of EGFR gene in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A31.