Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis

作者：Ross A. Soo, Byoung Chul Cho, Joo-Hang Kim, Myung‐Ju Ahn, Ki Hyeong Lee, Anastasia Zimina, Sergey Orlov, Igor Bondarenko, Yun‐Gyoo Lee, Yueh Ni Lim, Sung Sook Lee, Kyung-Hee Lee, Yong Kek Pang, Chin Heng Fong, Jin Hyoung Kang, Chun Sen Lim, Pongwut Danchaivijitr, Saadettin Kılıçkap, James Chih‐Hsin Yang, Çağatay Arslan, Hana Lee, Seong Nam Park, İrfan Çiçin · 发表于：Journal of Thoracic Oncology · 年份：2023 · DOI：10.1016/j.jtho.2023.08.017 · 被引用次数：31 · 研究领域：Brain Metastases and Treatment、Lung Cancer Treatments and Mutations、Head and Neck Cancer Studies

INTRODUCTION: 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...