Multicenter phase 2 trial of lazertinib for EGFR-variant non-small cell lung cancer with CNS failure of previous EGFR tyrosine kinase inhibitors

EGFR-variant non-small cell lung cancer (NSCLC) is associated with a high rate of central nervous system (CNS) metastases, even with treatment with first-generation or second-generation EGFR TKIs. Lazertinib is a third-generation EGFR TKI. A multicenter phase 2 trial in South Korea evaluated lazertinib in patients with EGFR-variant NSCLC who had brain metastases after unsuccessful treatment with first-generation or second-generation EGFR TKI. Among 38 for response evaluable patients (12 with leptomeningeal metastases) the intracranial objective response rate was 55% (95% CI 38.3-71.4), with responses seen in T790M-positive disease as well as T790M-negative and T790M-unknown disease. The median intracranial progression-free survival was 15.8 months (95% CI 15.2-NR). Most adverse events were grade 1 or 2. The authors conclude that lazertinib had substantial CNS activity in EGFR-variant mNSCLC patients with CNS failure of previous first-generation or second-generation EGFR TKI.