Lazertinib as Another First-Line Option for Patients With EGFR-Mutated, Advanced NSCLC

Results From the Phase 3 LASER301 Trial 

Findings from the global, double-blind, phase 3 LASER301 trial demonstrated that lazertinib, a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), significantly improved efficacy compared to gefitinib in the first-line setting among patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC).

According to Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, Republic of Korea, and coauthors, wrote “lazertinib is distinguished by its substituted pyrazole and morpholine groups and is more selective for mutant EGFR.”

In the LASER301 study, 393 patients were randomized on a 1-to-1 basis to receive either 240 mg lazertinib or 250 mg gefitinib with lazertinib- or gefitinib-matched placebo tablets until disease progression or treatment discontinuation. The primary end point was investigator assessed progression-free survival (PFS), assessed by RECISIT v 1.1 guidelines. Secondary end points included duration of response (DOR), overall survival (OS), and safety.

At the data cutoff date of July 29, 2022, the median PFS was 20.6 months in the lazertinib arm and 9.7 months in the gefitinib arm (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34 to 0.58; P < .001), with the PFS benefit of lazertinib over gefitinib consistent across all predefined subgroups. The median DOR in the lazertinib arm was 19.4 months vs 8.3 months in the gefitinib arm. Despite OS data being immature at interim analysis, the 18-month survival rates were 80% and 72%, respectively (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116).

In both treatment arms, safety was consistent with previously reported safety profiles, and patients experienced similar treatment-emergent adverse events. The most common adverse events of any cause included paresthesia, rash, pruritus, and diarrhea.

Journal of Clinical Oncology associate editor Thomas E. Stinchcombe, MD, Duke Cancer Center, Durham, North Carolina, stated these findings demonstrate “lazertinib…is another first-line treatment option for patients with EGFR-mutant NSCLC with either an exon 19 deletion or exon 21 L858R mutation.” According to Dr Cho and coauthors, “Ongoing research will evaluate lazertinib efficacy with other agents, such as amivantamab plus platinum-based chemotherapy, to determine lazertinib's positioning in the treatment paradigm for EGFRm NSCLC.”

Source: 

Cho B, Ahn MJ, Kang JH, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non–small-cell lung cancer: Results from LASER301. J Clin Oncol. Published online June 28, 2023. doi:10.1200/JCO.23.00515