Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis
Authors
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 Kilickap ; James Chih-Hsin Yang ; Cagatay Arslan ; Hana Lee ; Seong Nam Park ; Irfan Cicin
Citation
JOURNAL OF THORACIC ONCOLOGY, Vol.18(12) : 1756-1766, 2023-12
Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / genetics ; Central Nervous System ; ErbB Receptors / genetics ; Gefitinib / pharmacology ; Gefitinib / therapeutic use ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Mutation ; Protein Kinase Inhibitors / pharmacology ; Protein Kinase Inhibitors / therapeutic use ; Quinazolines / pharmacology
Keywords
CNS ; Lazertinib ; NSCLC ; TKI
Abstract
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 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 measurable CNS lesions, the intracranial objec- tive response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population. Conclusions: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free sur- vival compared with gefitinib, with more durable responses.