In a phase III trial (LASER301) reported in the Journal of Clinical Oncology, Byoung Chul Cho, MD, PhD, and colleagues found that lazertinib improved progression-free survival vs gefitinib in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC).
As stated by the investigators, “Lazertinib is a potent, central nervous system (CNS)-penetrant, mutant-selective, third-generation tyrosine kinase inhibitor that targets T790M and sensitizing mutations while sparing wild-type EGFR.”
Byoung Chul Cho, MD, PhD
In the double-blind trial, patients from sites in 13 Asian and European countries were screened between February 2020 and September 2021. A total of 393 patients with EGFR-mutated (exon 19 deletion/L858R) locally advanced or metastatic disease were randomly assigned to receive lazertinib at 240 mg once daily (n = 196) or gefitinib at 250 mg once daily (n = 197). Overall, 66% of patients in each group were Asian. Approximately 25% of patient had CNS metastases at entry. The primary endpoint was investigator-assessed progression-free survival.
Median follow-up was 20.5 months (interquartile range [IQR] = 15.2–23.3 months) in the lazertinib group and 20.6 months (IQR = 15.6–26.0 months) in the gefitinib group. Median progression-free survival was 20.6 months (95% confidence interval [CI] = 17.8–26.1 months) in the lazertinib group vs 9.7 months (95% CI = 9.2–11.3 months) in the gefitinib group (hazard ratio [HR] = 0.45, 95% CI = 0.34–0.58, P < .001). Hazard ratios favored the lazertinib group among both Asian patients (0.46, 95% CI = 0.34–0.63) and non-Asian patients (0.38, 95% CI = 0.23–0.64) and among those with (0.42, 95% CI = 0.26–0.68) and those without (0.44, 95% CI = 0.32–0.60) CNS metastases at entry.
Objective response was observed in 76% of patients in each group; median response duration was 19.4 months (95% CI = 16.6–24.9 months) with lazertinib vs 8.3 months (95% CI = 6.9–10.9 months) with gefitinib. Overall survival data were immature at time of progression-free survival analysis; overall survival at 18 months was 80% vs 72% (HR = 0.74, 95% CI = 0.51–1.08, P = .116).
The most common adverse events of any grade were paresthesia (39%), rash (36%), pruritus (27%), and diarrhea (26%) in the lazertinib group, and diarrhea (39%), rash (37%), increased alanine aminotransferase (30%), and increased aspartate aminotransferase (26%) in the gefitinib group. Grade ≥ 3 adverse events occurred in 41% vs 43% of patients. Adverse events led to discontinuation of treatment in 10% vs 9% of patients. One treatment-related death was observed due to interstitial lung disease in a patient receiving lazertinib.
The investigators concluded, “Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.”
Dr. Cho, of Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Yuhan Corporation. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.