P1.03 Case Series of Double Mutations in Patients with Lung Adenocarcinoma

Abstract

The introduction of targeted therapies has increased the survival time in a subset of patients with NSCLC. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology recommend measuring the local EGFR gene mutations of NSCLC patients before treatment. Sensitivity to EGFR TKIs in patients with double or multiple mutations is not well described. In the literature there are few reported cases of double mutations. We present a series of six cases of Lung Adenocarcinoma with double mutations found between 2006 and 2017 in a hospital in Northern MX. 450 patients with Lung cancer were evaluated from 2006 to 2017. DNA extraction is performed using a commercial extraction kit, the process is performed by real-time PCR on an automated platform in a closed circuit with a commercial panel. The DNA quantification quality control process is analyzed, validating with positive and negative controls, then analysis of the 29 known mutations of EGFR gene exons 18, 19, 20, 21. This study includes 450 patients, 141 (31.33%) patients had EGFR mutations, of which six (4.25%) had double exons EGFR mutations. Of the six cases with double mutations, male to female ratio was 1:1. The histological patterns reported in the double mutations were: 3 (50%) cases with acinar pattern, 2 (33.33%) with micropapillary pattern, and 1 (16.66%) solid pattern. The median age of the six patients is 54 years (range 38-78).Tabled 1First MutationSecond MutationHistological patternAge of patientCase #1L858RL861QAcinar52Case #2L858RExon 19 deletionMicropapillary55Case #3Exon 19 deletionL861QMicropapillary38Case #4Exon 19 deletionT790MSolid53Case #5Exon 19 deletionL861QAcinar78Case #6Exon 19 deletionL858RAcinar55 Open table in a new tab EGFR co-mutation had a significantly lower mean progression-free survival than those with a single mutation (5.7 months vs. 12.3 months). The response rate to TKI was significantly worse in those with co-mutation compared to those without co-mutation (38% vs 89%). There are few studies evaluating all the characteristics of cases with double mutations, such as histological pattern and the mutations of EGFR gene exons. Further research on double mutations is suggested because of the impact on treatment and prognosis of the patient.