Soo R.A.Cho B.C.Kim J.H.Ahn M.J.Lee K.H.Zimina A.Orlov S.Bondarenko I.Lee Y.G.Lim Y.N.Lee S.S.Lee K.H.Pang Y.K.Fong C.H.Kang J.H.Lim C.S.Danchaivijitr P.Kilickap S.Yang J.C.H.Arslan C.Lee H.Park S.N.Cicin I.Mahidol University2023-12-112023-12-112023-12-01Journal of Thoracic Oncology Vol.18 No.12 (2023) , 1756-176615560864https://repository.li.mahidol.ac.th/handle/20.500.14594/91416Introduction: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases. Methods: Treatment-naive patients with EGFR–mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response. Results: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8–28.2) versus 8.4 months (95% CI: 6.7–not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20–0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3–NR) versus 6.3 months (2.8–NR) with gefitinib. Tolerability was similar to the overall LASER301 population. Conclusions: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.MedicineConference PaperSCOPUS10.1016/j.jtho.2023.08.0172-s2.0-851775970781556138037865896