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

Study Details

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.

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).

Adverse Events

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.