Central Nervous System Outcomes of Lazertinib Treatment in EGFR-Mutated Advanced NSCLC: Pooled Analysis From LASER201 and LASER301
- PMID: 41067998
- DOI: 10.1016/j.cllc.2025.08.007
Central Nervous System Outcomes of Lazertinib Treatment in EGFR-Mutated Advanced NSCLC: Pooled Analysis From LASER201 and LASER301
Abstract
Background: Lazertinib, a brain-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), significantly improved efficacy in patients with treatment-naïve, EGFR-mutated advanced non-small cell lung cancer (NSCLC) in the clinical trials, LASER201 and LASER301. This analysis evaluated the efficacy and safety of lazertinib in patients with EGFR-mutated NSCLC and CNS metastases using pooled data from LASER201 and LASER301.
Patients and methods: Patients with treatment-naïve, EGFR-mutated advanced NSCLC and stable CNS metastases who were treated with lazertinib in a cohort of LASER201 and LASER301 were included. Intracranial progression-free survival (iPFS), intracranial objective response rate (iORR), intracranial disease control rate (iDCR), intracranial duration of response (iDoR), and treatment-emergent adverse events (TEAEs) were assessed.
Results: A total of 64 patients were included in the intracranial full analysis set (iFAS); 24 patients had at least 1 measurable CNS lesion at baseline. The median iPFS was 27.7 months (95% CI: 15.7-32.8) in the iFAS population. For patients with at least 1 measurable CNS lesion at baseline, iORR was 92% and iDCR was 96%. The median iDoR was 26.5 months (95% CI: 8.3-30.1). TEAEs were reported in 98% of patients in the iFAS population, with grade ≥3 TEAEs occurring in 55% of patients. The most common TEAEs were paresthesia (47%), rash (41%), and pruritus (36%).
Conclusion: In this pooled analysis of LASER201 and LASER301, lazertinib demonstrated a clinically meaningful treatment benefit and consistent safety profile in patients with EGFR-mutated advanced NSCLC and CNS metastases.
Keywords: Brain metastases; CNS; Lazertinib; NSCLC; TKI.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure James CH Yang reports financial support was provided by honoraria from Amgen (institution), AstraZeneca, AstraZeneca/MedImmune (institution), BeiGene (institution), Boehringer Ingelheim, Boehringer Ingelheim (institution), Bristol Myers Squibb, Daiichi Sankyo/AstraZeneca (institution), Dizal Pharma (institution), Gilead (institution), Lilly, MSD, MSD (institution), Novartis, Ono Pharmaceutical, Pfizer, Pfizer (institution), Roche, Roche/Genentech (institution), Sanofi/Regeneron (institution), Taiho Pharmaceutical (institution), Takeda, Takeda (institution); consulting or advisory role for AbbVie, AbbVie (institution), Amgen, Amgen (institution), ArriVent Biopharma (institution), AstraZeneca, AstraZeneca (institution), Bayer, Bayer (institution), Blueprint Medicines, Boehringer Ingelheim, Boehringer Ingelheim (institution), Bristol Myers Squibb, Celgene, Clovis Oncology, Daiichi Sankyo, Daiichi Sankyo/AstraZeneca (institution), G1 Therapeutics, Gilead (institution), GSK (institution), Hansoh, Incyte, Janssen (institution), Lilly (institution), Merck KGaA (institution), MSD, MSD (institution), Novartis, Novartis (institution), Ono Pharmaceutical, Pfizer, Pfizer (institution), Puma Biotechnology (institution), Roche/Genentech (institution), Sanofi (institution), Taiho Pharmaceutical (institution), Takeda, Takeda (institution), Yuhan Corporation; research funding from AstraZeneca (institution); travel, accommodations, expenses from Pfizer, AstraZeneca, Dizal Pharma. Myung-Ju Ahn reports financial support was provided for consulting for AstraZeneca, Yuhan Corporation, MSD, Takeda, Amgen, Daiichi Sankyo, Arcus, Alpha-Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Merck. Ji-Youn Han reports financial support was provided by consulting fees from AstraZeneca, AbbVie, LG Chem, Daewoong Pharma, Lantern, Janssen, Takeda, Roche, Amgen, Daiichi Sankyo, Oncovix, Novartis, Bristol Myers Squibb, Merck, Pfizer; honoraria from AstraZeneca, Takeda, Novartis, Pfizer, Janssen, Merck, Yuhan Corporation, Roche; payment for expert testimony from AstraZeneca; advisory role for Janssen, AstraZeneca. Ki Hyeong Lee reports financial support was provided for consulting or an advisory role for Bristol Myers Squibb, MSD, AstraZeneca, Pfizer, Lilly; research funding from Merck. Dong-Wan Kim reports financial support was provided by research funding to institution from Alpha Biopharma, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Bridge Biotherapeutics, Chong Kun Dang, Daiichi Sankyo, GSK, Hanmi, IMBdx, HK inno.N, IQVIA, Janssen, Merck, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, Turning Point Therapeutics, Xcovery, Yuhan Corporation; medical writing assistance from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Bridge Biotherapeutics, Chong Kun Dang, Daiichi Sankyo, GSK, IMBdx, Janssen, Merus, Mirati Therapeutics, MSD, Merck, Novartis, Pfizer, Roche, Takeda, Yuhan Corporation. Chun Sen Lim reports financial support was provided by honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Pfizer, Roche, Sanofi/Regeneron (institution), Takeda. Young Joo Min reports financial support was provided for consulting for Bristol Myers Squibb, Pfizer, AstraZeneca, MSD, Yuhan Corporation. Youngjoo Lee reports financial support was provided by consulting fee from AstraZeneca, Roche, Merck, Yuhan Corporation, Bayer, Amgen. YuKyung Kim reports financial support was provided by employment with Yuhan Corporation. Mi-Jung Kwon reports financial support was provided by employment with Yuhan Corporation. Hana Lee reports financial support was provided by employment with Yuhan Corporation. Hyeonchae Cho reports financial support was provided by employment with Yuhan Corporation. Byoung Chul Cho reports financial support was provided by grants or research support from GI Innovation, AstraZeneca, Champions Oncology, CJ Bioscience, Cyrus Therapeutics, Janssen, MSD, Dong-A ST, Yuhan Corporation, ImmuneOncia, Therapex, J INTS BIO, Vertical Bio AG; royalties from Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; consulting fees from BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, CJ, Cyrus Therapeutics, Ono Pharmaceutical, Yuhan Corporation, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Gilead, Amgen, Daiichi Sankyo, Regeneron, Sanofi, AnHeart Therapeutics, Seagen, Harpoon Therapeutics, GSK, ArriVent; invited speaker for American Society of Clinical Oncology (ASCO), AstraZeneca, Guardant Health, Roche, European Society for Medical Oncology (ESMO), International Association for the Study of Lung Cancer (IASLC), Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Zai Lab; advisory role for Kanaph Therapeutics, Bridge Biotherapeutics, Cyrus Therapeutics, Guardant Health, J INTS BIO, Therapex; member of the board of directors for J INTS BIO; stock ownership with Theravance, Gencurix, Bridge Biotherapeutics, Kanaph Therapeutics, Cyrus Therapeutics, Interpark Bio Convergence Corp., J INTS BIO; employment with Yonsei University Health System; founder of DAAN Biotherapeutics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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