Abstract B02: Liquid biopsy for screening of driver mutations in EGFR gene: Personalized medicine for use tyrosine kinase inhibitors in non-small cell lung cancer patients

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers worldwide. In Brazil there were an estimated 28.220 new cases in 2016. The 5-year survival rate in advanced NSCLC patients is less than 5%, making necessary the development of diagnostic strategies to improve the treatment and survival of these patients. Activating mutations of epidermal growth factor receptor (EGFR) gene occur in approximately 10–15 % in Caucasian and approximately 30% in Brazilian NSCLC cases. The first- and second-generation of EGFR tyrosine kinase inhibitors (TKIs) have been widely used for advanced NSCLC patients who are eligible for the treatment. Liquid biopsies using plasma-derived cell-free DNA (cfDNA) is an emerging noninvasive test allowing a better selection and monitoring of NSCLC. The aim of this study was to evaluate the frequency of EGFR mutations using liquid biopsy samples before and after TKIs treatment in a cohort of NSCLC Brazilian patients. All the patients were investigated for EGFR mutations by real-time qPCR Cobas© EGFR Mutation Test v2. Clinical data were obtained prior to blood collection from physician and/or pathologists involved in the original diagnoses. Blood samples were collected at Progenetica Laboratory or sent from other laboratories, centrifuged immediately for the plasma separation, and frozen. Fisher´s exact test was calculated to compare frequency distribution between two groups (GraphPad Prism version 6.00). This study enrolled 535 NSCLC Brazilian patients from Southeast+South (74.9%), North+Northeast (8.8%), and Midwest+Federal District (4.7%). Regional information was missing for 11.3% of cases. As expected, NSCLC was more frequent among women (56.4%) compared to men (43.6%). Four hundred cases (74.8%) did not show any EGFR mutations; however, 135 cases presented 19Del (57.8%), L858R (16.3%), double 19Del; T790M (11.1%), double T790M; L858R (8.15%), G719X (2.9%), L861Q (1.48%), 20Ins, triple L858R; T790M; 20Ins and S768I; G719X (0.74% each one) mutations spanning 18, 19, 20, and 21 EGFR exons. Previous results from liquid biopsy for EGFR mutation were obtained for 75/535 cases (14%). Among these patients, 10/75 cases (13.3%) presented nondetected mutations. Deletions at exon 19 (19Del) and mutations at exon 21 (L858R) were the most frequent, accounting for 61.5% and 23%, respectively. Since 19Del and L858R are drug-sensitive mutations, we compared the frequency of EGFR mutations in patients before and after TKIs