P1.02-010 Frequency of Uncommon EGFR Mutations in NSCLC in an Argentinean University Institution

Abstract

EGFR mutations are present in approximately 15% of NSCLC Caucasian patients, with a similar frequency described in Argentina. Exon 19 deletions and exon 21 L858R are consider common mutations (>90 %) that predict better progression free survival with EGFR-TKIs than with chemotherapy treatment. Most relevant uncommon mutations had a frequency ranged from 1.9% to 7.9% between different populations and their outcome, in general, is less favorable. We analyzed, retrospectively, our dataset of EGFR mutational status in the last two years with the objective to describe the frequency and characteristics of the patients with uncommon EGFR mutations in our population of NSCLC patients. The mutational analysis was performed on formalin fixed paraffin-embedded tissue blocks. EGFR exons 18 through 21 were amplified by PCR- based technology. A total of 113 patients underwent EGFR testing since January 2014 until June 2016. Among them, 29 cases (25.7 %) harbored EGFR mutations. The exon 19 deletions (n=9; 8%) and L858R point mutation (n=6; 5.3%) accounted for the 51.7 % of EGFR mutated cases (13.3% of the population explored) while 48.3 % were uncommon mutations (12,4%). In the last group, mutations sites were: G719X in exon 18 (n=9; 8%), L861Q in exon 21 (n=2; 1.8%), INS20 in exon 20 (n=2; 1.8%) and S768I in exon 20 (n=1; 0.9%). All the 14 patients carrying EGFR uncommon mutations had adenocarcinoma histology. In addition, they were more frequently observed in men than in women (79% versus 21%) and in smokers than in nonsmokers (65% versus 45%). The mean age was 62.5 years. Most of the patients (n=11; 75.6%) had advanced disease (stage IIIB-IV) at diagnosis. No one had Asian ethnicity. Seven patients (50%) received EGFR-TKIs for first or second line treatment (4 erlotinib, 2 afatinib and 1 gefitinib). None of them showed sustained clinical benefit. At present, 7 out of 12 patients had died. Although the clinical characteristics of our cohort are similar to the data published, we noted a higher and unusual frequency of EGFR uncommon mutations especially exon 18 G719X.All cases treated with EGFR-TKIs showed poor sensitivity to therapy. Time to treatment and accessibility to appropriate therapy in this subgroup are important issues to explore in future reports from public institutions of our region.