Survival outcomes and symptomatic central nervous system (CNS) metastasis in EGFR-mutant advanced non-small cell lung cancer without baseline CNS metastasis: Osimertinib vs. first-generation EGFR tyrosine kinase inhibitors

Central nervous system (CNS) metastases are common complications in epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (TKIs). However, for patients without baseline CNS metastasis, data regarding the incidence of symptomatic CNS metastasis with EGFR-TKI treatment and its risk factors are still rare.Patients with EGFR-mutant advanced NSCLC without baseline CNS metastasis who are receiving first- and/or third-generation EGFR-TKIs were included. Overall survival (OS), cumulative incidence of symptomatic CNS metastasis upon treatment failure, and their risk factors were evaluated.There were 813 patients enrolled, with 562, 106, and 32 received first-line gefitinib, erlotinib, and osimertinib, respectively, while 113 received second-line osimertinib. At a median follow-up of 18.1 months, the median OS was 45.5 months. There were 38 patients developed symptomatic CNS metastases. Osimertinib-treated patients tended to have a lower risk of CNS metastases compared with those treated with first-generation EGFR-TKIs (p = 0.059). However, the cumulative incidence curves of symptomatic CNS metastasis tended to reach a plateau after approximately 3 years regardless of which generation was used, and incidences beyond that period were similar in the two groups. Patients with L858R mutation exhibited a higher risk of developing CNS metastasis than patients with 19del mutation (p = 0.001). Interestingly, the presence of baseline neuroimaging was not associated with the risk of developing CNS metastasis or OS.Compared with first-generation EGFR-TKIs, osimertinib can delay but not prevent the development of symptomatic CNS metastasis. L858R mutation is an independent risk factor for CNS metastasis.