Cho B.C.Ahn M.J.Kang J.H.Soo R.A.Reungwetwattana T.Yang J.C.H.Cicin I.Kim D.W.Wu Y.L.Lu S.Lee K.H.Pang Y.K.Zimina A.Fong C.H.Poddubskaya E.Sezer A.How S.H.Danchaivijitr P.Kim Y.Lim Y.An T.Lee H.Byun H.M.Zaric B.Mahidol University2023-09-152023-09-152023-09-10Journal of clinical oncology : official journal of the American Society of Clinical Oncology Vol.41 No.26 (2023) , 4208-4217https://repository.li.mahidol.ac.th/handle/20.500.14594/90011PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS: 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 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .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. Overall survival 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 = .116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1200/JCO.23.005152-s2.0-851701123491527775537379502