EPIDEMIOLOGY OF CENTRAL NERVOUS SYSTEM METASTASES IN PATIENTS WITH LUNG ADENOCARCINOMA HARBORING ONCOGENIC DRIVER ALTERATIONS

Introduction: Lung cancer is the leading cause of cancer-related mortality worldwide. Numerous oncogenic driver alterations associated with non-small cell lung cancer (NSCLC) have been described lately. A breadth of targeted therapies has changed the treatment paradigm for NSCLC. Despite these advances, NSCLC remains a lethal disease, with central nervous system metastases (CNSm) being one of the main causes of death. Data regarding the frequency of molecular alterations, clinical characteristics, and treatment sequencing in patients with NSCLC and CNSm harboring actionable targets are scarce in the Brazilian population. Objective: To describe molecular profiling, clinical and epidemiological characteristics of lung adenocarcinoma (LA) patients harboring oncogenic driver alterations, diagnosed with CNSm during their clinical history. Methods: Retrospective study of data extracted from patient electronic records from a single institution. Patients with LA and oncogenic driver alterations were selected. Those with evidence of CNSm were included for analysis. Clinical and molecular characteristics were described. Results: We identified 313 patients with LA and driver genetic alterations. CNSm were detected in 131 patients (41.8%), 79 women and 52 men. At diagnosis, median age was 58 years and 86.3% had an ECOG performance status of 0 or 1. Most individuals were never smokers (48.9%) and 53.4% had CNS involvement on initial presentation. Overall, EGFR activating mutations were the most frequent (62.1%), followed by ALK rearrangement (16.7%), KRAS mutation (9.8%), MET mutation (4.5%) and RET rearrangement (3.0%). Only 1.5% of patients showed genetic alterations in ROS1 and BRAF. Mutations in HER2 were very uncommon (0.8%). The majority of patients (47.3%) received cytotoxic chemotherapy as first-line systemic treatment and targeted therapy (TKIs) afterwards. Local therapies for brain metastases were performed in 69.5%. Conclusion: Our findings were somewhat concordant with those of international databases. We found a high frequency of EGFR mutations in this population, possibly explained by the longer life expectancy of these patients. Many of the patients were treated with systemic and local therapies, reflecting our institution standard approach to CNSm. A prospective analysis is required to better determine the prognostic value of these findings and their correlation with different outcomes.