Cancer Therapy: Clinical The Impact of Initial Gefitinib or Erlotinib versus Chemotherapy on Central Nervous System Progression in Advanced Non–Small Cell Lung Cancer withEGFRMutations

Purpose: This retrospective studywas undertaken to investigate the impact of initial gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) versus chemotherapy on the risk of central nervous system (CNS) progression in advanced non–small cell lung cancer (NSCLC) with EGFR mutations. Experimental Design: Patients with stage IV or relapsed NSCLC with a sensitizing EGFR mutation initially treated with gefitinib, erlotinib, or chemotherapy were identified. The cumulative risk of CNS progression was calculated using death as a competing risk. Results:One hundred and fifty-five patients were eligible (EGFR-TKI: 101, chemotherapy: 54). Twentyfour patients (24%) in the EGFR-TKI group and 12 patients (22%) in the chemotherapy group had brain metastases at the time of diagnosis of advanced NSCLC (P 1⁄4 1.000); 32 of the 36 received CNS therapy before initiating systemic treatment. Thirty-three patients (33%) in the EGFR-TKI group and 26 patients (48%) in the chemotherapy group developed CNS progression after a median follow-up of 25months. The 6-, 12-, and 24-month cumulative risk of CNS progression was 1%, 6%, and 21% in the EGFR-TKI group compared with corresponding rates of 7%, 19%, and 32% in the chemotherapy group (P1⁄4 0.026). The HR of CNS progression for upfront EGFR-TKI versus chemotherapy was 0.56 [95% confidence interval (CI),