Epidermal growth factor receptor (EGFR) mutations detected by denaturing high performance liquid chromatography (dHPLC) in non-small cell lung cancer (NSCLC): Correlation with disease stage and response to tyrosine kinase inhibitors (TKI) therapy

Abstract

22118 Background: Somatic mutations of the EGFR gene predict sensitivity to EGFR-TKI in NSCLC patients. dHPLC is a sensitive method for detecting EGFR mutations in NSCLC tumours. The goal of this study was to investigate the relationship between EGFR status (mutation and type) and disease stage and response to TKI therapy. Methods: All patients (pts) diagnosed with NSCLC in 2005 were identified and genotyped for EGFR exons 19 and 21 mutations using dHPLC. Results were correlated with the stage of disease. In addition, all genotyped tumours were correlated with patient demographics, smoking status, tumor histology, disease stage, response to TKI, and overall survival. Results: 144 pts were diagnosed with NSCLC at our institution in 2005. 62 pts were genotyped, 82 are still pending. Our preliminary data show 34% (10/29) of pts with advanced disease (stage 3B/4) were mutation positive compared with 6% (2/33) of early stage disease (p=0.007). Since 2004 we have genotyped a total of 228 NSCLC pts. Using dHPLC, we identified mutations in 26% of tumour samples (59 of 228). Mutations were more common in women, non-smokers, adenocarcinomas, and late stage disease. 50 out of 157 patients with advanced NSCLC received TKI therapy. Of these, 17 had mutations on exon 19 and 4 on exon 21. Patients with EGFR mutations were more likely to benefit (partial response or stable disease) from TKI therapy (76% vs 31%; p=0.002). There was a trend towards better survival in patients with exon 19 mutations regardless of therapy. Conclusion: dHPLC is a sensitive and reliable test for EGFR mutation identification. EGFR mutations seem to be more common in advanced disease, although full genotyping is still ongoing and final results will be presented. Pts with EGFR mutations were more likely to benefit from TKI therapy. The presence of an exon 19 deletion appears to be a good prognostic factor regardless of therapy. These observations warrant further confirmation in large prospective studies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Canada