Central Nervous System Activity of Lazertinib in EGFR ‐Mutated NSCLC With Prior EGFR TKI Exposure: A Pooled Analysis of KCSG‐LU20‐15 and LU21‐01

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ABSTRACT Background Central nervous system (CNS) involvement remains a major cause of mortality in patients with epidermal growth factor receptor (EGFR)‐mutated nonsmall cell lung cancer (NSCLC), particularly, after progression on EGFR tyrosine kinase inhibitors (TKIs). This pooled analysis evaluated the efficacy of lazertinib in patients with EGFR ‐mutated NSCLC and CNS involvement, using data from two Phase II trials. Patients and Methods Patients with EGFR ‐mutated NSCLC and CNS involvement following prior EGFR TKI therapy enrolled in the KCSG‐LU20‐15 and KCSG‐LU21‐01 were included. Overall and intracranial objective response rate (ORR), disease control rate (DCR), and progression‐free survival (PFS) were assessed. Results Seventy‐two patients were included. The median age was 63 years and 45 patients (62.5%) had leptomeningeal metastases (LM). T790M status was positive in 7 patients, negative in 44, and unknown in 21. Intracranial tumor responses were evaluable in 46 patients; the intracranial ORR was 50.0%, and the intracranial DCR was 97.8%. The median intracranial PFS was 15.2 months. Among 66 patients evaluable for systemic response, the overall ORR and DCR were 22.7% and 97.0%, respectively. The median PFS and overall survival were 10.6 and 17.8 months, respectively. Patients with LM experienced inferior OS and intracranial PFS compared with those without LM. No significant differences in clinical outcomes were observed according to T790M status. Conclusion Lazertinib demonstrated meaningful CNS activity in patients with EGFR ‐mutated NSCLC and CNS involvement after prior EGFR TKI exposure, including those with LM. Notably, this activity was observed in a cohort with a low prevalence of confirmed T790M positivity.