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. © 2025 The Authors.