P76.13 Osimertinib Delays but Not Prevents Central Nervous System Metastasis in EGFR-Mutant Advanced Non-Small Cell Lung Cancer

Abstract

Central nervous system (CNS) is a common site of EGFR Tyrosine kinase inhibitor (TKI) treatment failure in advanced non-small cell lung cancer (NSCLC). Various EGFR TKIs with distinct potencies against CNS metastasis are approved. This study aims to compare the incidence of symptomatic CNS metastasis in advanced EGFR-mutant NSCLC without baseline CNS lesions and receiving first- or third-generation EGFR TKIs. Patients with EGFR-mutant advanced NSCLC without baseline CNS metastasis and receiving standard of care EGFR-TKIs were included. Cumulative incidences of symptomatic CNS metastasis upon EGFR-TKI treatment failure were calculated using the Kaplan-Meier method and significant risk factors of CNS metastasis were identified using the Cox proportional hazards models. Furthermore, radiographic features and clinical outcomes of patients who developed CNS metastasis were analyzed. Among 935 patients enrolled, 633, 143 and 35 received first-line gefitinib, erlotinib and osimertinib, respectively, and the remaining 124 received second-line Osimertinib. At a median follow-up of 10 months (range, 1-93 months), 517 patients developed EGFR-TKI treatment failure, of whom 45 had symptomatic CNS metastasis. The 1-, 2- and 3-year cumulative incidences of symptomatic CNS metastasis were 4.2%, 7.9% and 14.4%, respectively. There was no difference of developing symptomatic CNS metastasis among patients receiving gefitinib or erlotinib (p=0.857), while patients receiving osimertinib (Group B) had a significant lower risk than those receiving first-generation EGFR-TKIs (Group A) (HR 0.45; 95%CI 0.20-0.99, p=0.049). Of note, the survival curves tended to reach a plateau after three years, and the cumulative incidence of symptomatic CNS metastasis beyond that time, as well as the percentage of patients who developed symptomatic CNS metastasis among those who had EGFR-TKI treatment failure, was similar in Group A and Group B. Patients harboring L858R mutation had a higher risk developing symptomatic CNS metastasis than patients harboring other types of sensitizing EGFR mutations (p=0.003). Among 45 patients who developed symptomatic CNS metastasis, 20 had single cranial lesion, 39 had a largest tumor lesion smaller than 3cm and 39 had metastatic lesion outside the hippocampus region. Moreover, among the 45 patients, median overall survival (OS) calculated from the diagnosis of advanced disease was 33.3 (95%CI 24.8-41.8) months, and patients with single cranial lesion had a significantly longer OS (p=0.011). Compared with first-generation EGFR-TKIs, osimertinib significantly delays the development of symptomatic CNS metastasis in EGFR-mutant advanced NSCLC and L858R mutation is an independent risk factor of CNS metastasis.