FREQUENCY OF EGFR EXON 20 INSERTIONS IN BRAZILIAN LUNG ADENOCARCINOMA PATIENTS

Introduction: In the last years, targeted therapies have revolutionized the clinical management of non-small lung cancer (NSCLC) patients as EGFR inhibitors. However, insertions in the exon 20 of the EGFR gene lead to resistance in patients treated with EGFR inhibitors. Thus, new targeted therapies have emerged and could benefit NSCL patients harboring EGFR ex20ins. AIMS: To evaluate the frequency of EGFR ex20ins and their clinicopathological and molecular features in a series of Brazilian lung adenocarcinoma patients. MATERIALS AND Methods: We analyzed 1598 lung adenocarcinoma Brazilian patients that were indicated for lung cancer molecular testing at the Department of Molecular Diagnosis from 2010 to 2022. The EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). Clinicopathological and molecular data were collected from patients’ medical records. The frequency of mutations and clinicopathological features was obtained using IBM SPSS version 22. Results: From the 1598 lung adenocarcinoma patients, most were male (53.4%), quitter, or current smokers (66.6%), and diagnosed with advanced stage (67.2%) with a median age of 63.0 years. In addition, EGFR mutations were associated with males, never smokers, and the presence of metastasis at diagnosis. Molecularly, 22.5%(n=360/1598) of patients were harboring EGFR mutations, and 1.7%(n=28/1598) of these mutations were ex20ins. Out of mutant EGFR patients harboring ex20ins, the most frequent mutation was the p.A767_V769dup (n=5/28) and the p.N771_H773dupNPH (n=4/28). Half of the patients with EGFR exon 20 insertions identified by next-generation sequencing (n=15/28) were also harboring TP53 mutations (n=7/15). In addition, from patients with EGFR exon 20 insertions identified by Direct Sanger Sequencing (n=10/28), 3 of them had no exon 20 insertions identified when analyzed Cobas technology. Conclusion: We observed that approximately 1.7% of patients harbor EGFR ex20ins mutations in our series and could be benefited from new treatments targeting these insertions.