EP1.14-32 Pattern of EGFR Mutations and Response to First Generation EGFR TKIs in Patients of Metastatic Lung Cancer at a Tertiary Care Centre in India

Abstract

EGFR gene mutations, ALK and ROS1 gene rearrangements represent the most common targetable lesions in the era of TKIs for treatment of metastatic lung cancer. Use of TKIs improves overall survival compared to cytotoxic chemotherapy in these patients. The objective of the study was to identify the prevalence and pattern of EGFR mutations and their response to TKIs in Indian patients. Histopathologically confirmed cases of metastatic lung adenocarcinoma diagnosed between 2016 to 2018 at Kidwai Cancer Institute, Bangalore were reviewed for their EGFR mutation, ALK and ROS1 gene rearrangement status. DNA was extracted from formalin fixed paraffin embedded tissue and tested for EGFR hotspot mutations (Exon 19 deletions, exon 20 insertions and substitution mutations G719X, S768I, T790M, L858R and L861Q in exons 18, 20 and 21 of the EGFR gene) using ARMS real-time PCR. ALK and ROS1 rearrangement was tested using IHC with primary antibody ALK D5F3 and ROS1 D4D6 respectively. Tabled 1Complex EGFR mutationsPATIENT IDEGFR MUTATIONTREATMENTPFS ( MTHS)51EXON 19 DEL + T790MChemotherapy61626EXON 19 DEL + L858RGefitinib6164S768I + L858RGefitinib2208L858R + T790MChemotherapy3229EXON 19 DEL + T790MChemotherapy4 Open table in a new tab A total of 240 patients underwent testing. EGFR mutations were detected in 31.6% (n =76) and ALK and ROS1 rearrangement in 7% (n=17) and 1.25% (n=3) of the patients. The most common EGFR mutation was exon 19 deletions (e19 del) (n=44; 57.9%) followed by L858R mutation in exon 21 (n=23; 30.3%). Double EGFR mutations was seen in 5 patients (6.6%) and 3 patients had L861Q mutation. One patient had upfront T790M mutation. Median age was 54 years (range 35 -78 years). Male to female ratio was 0.9. 43.45% (n=33) were never smokers. Gefitinib was advised in 50 patients (65.8%), Erlotinib in 21 patients (27.6%) and rest were treated with chemotherapy. Median PFS in patients with e19 del, L858R and other mutations was 11, 12 and 4 months respectively. The prevalence of EGFR mutations in our studies are similar to those reported from other parts of India, lower than that from other Asian countries and higher than that from Western countries. E19 del and L858R mutations respond favourably to TKIs, but complex mutations do so poorly. Use of TKIs other than Gefitinib and Erlotinib need to be explored in these cases to improve outcomes.