Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study
Ji-Youn Han,
Myung-Ju Ahn,
Ki Hyeong Lee,
Yun-Gyoo Lee,
Dong-Wan Kim,
Young Joo Min,
Sang-We Kim,
Eun Kyung Cho,
Joo-Hang Kim,
Gyeong-Won Lee,
Sung Sook Lee,
Na Mi Lee,
Hyun Woo Jang,
Heewon Han,
Hyejoo Park,
Jieon Lee,
Byoung Chul Cho
Affiliations
Ji-Youn Han
Division of Hemato-Oncology, Center for Lung Cancer, Research Institute and Hospital, National Cancer Center
Myung-Ju Ahn
Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine
Ki Hyeong Lee
Division of Medical Oncology, Department of Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine
Yun-Gyoo Lee
Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
Dong-Wan Kim
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital
Young Joo Min
Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine
Sang-We Kim
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
Eun Kyung Cho
Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine
Joo-Hang Kim
Division of Hematology-Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University
Gyeong-Won Lee
Division of Hematology and Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine
Sung Sook Lee
Department of Hematology-Oncology, Inje University Haeundae Paik Hospital, Inje University College of Medicine
Na Mi Lee
Clinical Development and Medical Division, Yuhan Corporation
Hyun Woo Jang
Clinical Development and Medical Division, Yuhan Corporation
Heewon Han
Clinical Development and Medical Division, Yuhan Corporation
Hyejoo Park
Clinical Development and Medical Division, Yuhan Corporation
Jieon Lee
Clinical Development and Medical Division, Yuhan Corporation
Byoung Chul Cho
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine
Abstract Background Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Methods Eligible patients were aged ≥ 20 years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240 mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. Results This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9 months; estimated survival rates at 12, 24, and 36 months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240 mg/day was consistent with previous findings. Conclusions Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. Trial registration ClinicalTrials.gov identifier NCT03046992.
