The global, randomised LASER301 study showed that patients with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC) receiving a third generation tyrosine kinase inhibitor (TKI) lazertinib had significantly longer progression-free survival (PFS) versus gefitinib, with a 55% lower risk of disease progression or death. Safety findings were consistent with prior reports.

LASER301 results build on the first-in-human phase I/II LASER201 study that demonstrated lazertinib 240 mg once daily had durable antitumour efficacy with clinically meaningful activity in patients with brain metastases. Findings from the LASER301 are published by Dr. Byoung Chul Cho of the Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Republic of Korea, and colleagues on 28 June 2023 in the Journal of Clinical Oncology.

The authors wrote in the background that the worldwide incidence rate of EGFR-mutated NSCLC is 32%, with 15% occurring in Europe and the highest rate (47%) occurring in the Asia Pacific region. While the introduction of first and second generation TKIs revolutionised the treatment of advanced EGFR-mutated NSCLC, tumours invariably acquire resistance, often via T790M secondary mutation.

Osimertinib was the initial third generation TKI to demonstrate clinical activity against EGFR T790M, exon 19 deletion, and L858R mutations. Lazertinib is a potent, central nervous system (CNS) active, mutation selective, third generation TKI that targets T790M and sensitising mutations while sparing wild-type EGFR. Preclinical studies demonstrated several potential differentiators of lazertinib over osimertinib.

In the phase I/II LASER201 study, lazertinib was associated with an overall response rate (ORR) of 55%, median PFS of 11.1 months, and median overall survival (OS) of 38.9 months in 76 patients with EGFR T790M NSCLC treated with prior early generation TKIs. In patients with asymptomatic CNS metastases, the median intracranial PFS was 26.0 months, intracranial ORR was 86%, median duration of intracranial response was 15.1 months, and the intracranial disease control rate (DCR) was 100%. No differences in OS were seen between patients with or without CNS metastases. In a cohort of treatment-naïve patients, the ORR was 70%, and median PFS was 24.6 months.

A randomised, double-blind, multinational phase III LASER301 study assessed the efficacy and safety of lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion/L858R) locally advanced or metastatic NSCLC.  Patients were ≥18 years with no prior systemic anticancer therapy. Patients with neurologically stable CNS metastases were allowed. Patients were randomised 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary endpoint was investigator-assessed PFS by RECIST version 1.1.

Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib, 20.6 versus 9.7 months (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.34 to 0.58; p < 0.001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups.

The objective response rate was 76% in both groups (odds ratio 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI 6.9 to 10.9) with gefitinib. OS data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR 0.74, 95% CI 0.51 to 1.08; p = 0.116).

Observed safety of both treatments was consistent with their previously reported safety profiles.

The authors commented that LASER301 efficacy is comparable with that in the FLAURA study, where first-line treatment with osimertinib provided significantly longer PFS versus erlotinib/gefitinib overall and in subgroups with or without baseline CNS metastases and with exon 19 deletion or L858R mutations. Lazertinib, a third generation EGFR TKI, is another first-line treatment option for patients with EGFR mutated NSCLC with either an exon 19 deletion or exon 21 L858R mutation.

The study was previously presented in part at the ESMO Asia 2022 Congress (2-4 December 2022, Singapore).

The study was funded by Yuhan Corporation.


Chul Cho B, Ahn M-J, Hyoung Kang J, et al. Lazertinib Versus Gefitinib as First-line Treatment in Patients With EGFR-mutated Advanced Non-Small Cell Lung Cancer (NSCLC): Results From LASER301. JCO; Published online 28 June 2023. DOI: 10.1200/JCO.23.00515