뇌전이가 동반된 EGFR 돌연변이 양성 비소세포 폐암 초치료 환자에서 Lazertinib의 유효성 연구 = Efficacy of Lazertinib in treatment-naive patients for EGFR mutated NSCLC with brain metastases

다국어 초록 (Multilingual Abstract)

Background Non–small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is frequently complicated by brain metastases; however, patients with symptomatic brain metastases are often excluded from clinical trials, resulting in limited evidence to guide optimal management. We investigated the efficacy of the third-generation EGFR tyrosine kinase inhibitor lazertinib in patients with EGFR-mutated NSCLC and both symptomatic and asymptomatic brain metastases. Methods This was a single-center, open-label, single-arm phase II study. Patients with symptomatic or asymptomatic brain metastases received oral lazertinib 240 mg once daily. Local treatment including surgery, focal radiotherapy, or whole-brain radiotherapy was administered based on multidisciplinary team recommendations. The primary endpoint was progression-free survival (PFS). Secondary endpoints included changes in symptoms assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline and first disease evaluation. Results A total of 75 patients were enrolled; 38 (50.7%) had neurologic symptoms at baseline. The median age was 65 years, 69.3% were female, and 25.3% had a history of smoking. EGFR mutation types included exon 19 deletion (53.3%) and L858R (46.7%). Lazertinib monotherapy was administered to 56 patients, while 19 received combined local treatment (surgery in 2, focal radiotherapy in 8, and whole-brain radiotherapy in 9). After a median follow-up of 13.6 months, the median PFS was 13.6 months (95% confidence interval [CI], 12.1–19.1), with no significant difference between symptomatic and asymptomatic patients (both 13.6 months; log-rank P = 0.935). Most adverse events (82.7%) were grade 1 or 2, with paresthesia (71%) and skin rash (71%) being the most common. Eight patients discontinued therapy due to adverse events. Except for diarrhea and nausea/vomiting, all EORTC QLQ-C30 symptom scores improved at first disease evaluation. Conclusions Lazertinib, with or without local therapy, demonstrated comparable PFS regardless of the presence of neurologic symptoms and was effective even in patients with neurologically unstable disease. The treatment exhibited an acceptable safety profile and contributed to symptomatic improvement. These findings support lazertinib as a viable therapeutic option for patients with EGFR-mutated NSCLC with brain metastases, including those with symptomatic presentations. Keywords: brain metastases, epidermal growth factor receptor mutation, lazertinib, non- small cell lung cancer, tyrosine kinase inhibitor Student number: 20245423

목차 (Table of Contents)

• Summary i
• List of Tables iv
• List of Figures v
• List of Abbreviations vi
• Introduction 1
• Methods 3
• Results 9
• Discussion 35
• Conclusion 39
• References 40
• 국문요약 43