FIRST-GENERATION EGFR-TKIS IN LUNG ADENOCARCINOMA HARBORING EGFR ACTIVATING MUTATIONS: LONG-TERM SURVIVAL PATIENTS

Introduction: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), is the most frequently chosen first-line treatment for lung adenocarcinoma patients harboring EGFR activating mutations (del19 and L858R), mainly due to its antineoplastic activity and toxicity profile. However, some patients may present prolonged survival, long-term clinical benefit, and/or absence of disease progression even when treated with first-generation EGFR-TKIs. Objectives To describe advanced lung adenocarcinoma patients’ characteristics who harbor EGFR activating mutations and whose overall survival was superior to 30 months under first-generation EGFR-TKIs. Methods: In our retrospective cohort of 98 patients with advanced lung adenocarcinoma harboring EGFR activating mutations, those who attained an overall survival over 30 months using first-generation EGFR-TKIs were considered long-term survivals (LTS). EGFR activating mutations were diagnosed in formalin-fixed and paraffin-embedded samples by direct sequencing (Sanger’s method) between 2011 and 2014. TTF-1 expression was evaluated by immunohistochemistry and considered positive if present in the nuclei of at least 10% of the evaluated cells. Overall survival was estimated by the Kaplan-Meier method and prognostic variables compared by log-rank. Frequencies were compared by chi-square or Fisher’s test when appropriate. Results: were considered significant if p-value was <0.05 (two-tailed). Results: Thirty-three patients (34%) were identified as LTS, with a median age of 67 years (43-97). Most were female (79%), and never smokers (79%). EGFR activating mutations were diagnosed as del19 (26 pts, 79%) and L858R (7 pts, 21%), and TTF-1 immunoexpression was considered positive in 83% of cases when evaluated. Patients were treated with first-generation EGFR-s (gefitinib or erlotinib) as a first (36%), second (45%), or third-line treatment (18%). At a median follow-up of 47.3 months, the median overall survival was 58 months for these 33 pts. Never-smoker status (p=0.001) and positive TTF-1 immunoexpression (p=0.0007) were associated with LTS. Conclusion: First-generation EGFR-TKIs may offer prolonged overall survival to a significant fraction of patients with lung adenocarcinoma harboring EGFR activating mutations in a real world scenario.