KEY TAKEAWAYS
- The LASER301 phase III trial aimed to assess the efficacy and safety of lazertinib compared to gefitinib in EGFR-mutated NSCLC for first-line treatment.
- The primary endpoint was investigator-assessed PFS. Secondary endpoints included OS, ORR, DoR, and safety.
- The result demonstrated lazertinib’s efficacy advantage over gefitinib in Asian patients with EGFR-mutated NSCLC, maintaining comparable safety.
Third-generation epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) Lazertinib tackles both mutant and T790M-resistant EGFR in nonsmall cell lung cancer(NSCLC), unlike osimertinib, which fell short in Asian and L858R subgroups despite extending PFS.
This highlighted the need for better options, especially for these patients. Researchers aimed to assess the efficacy and safety of lazertinib compared to gefitinib in EGFR-mutated NSCLC for first-line treatment.
The study included treatment-naïve patients with EGFR-mutated (exon 19 deletion [Ex19del]/L858R) locally advanced or metastatic NSCLC. Patients were randomly assigned in a 1:1 ratio to receive either lazertinib (240 mg oral [po]/day) or gefitinib (250 mg po/day).
The primary endpoint was progression-free survival (PFS), evaluated through Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety.
Key inclusion criteria involved the presence of EGFR mutations confirmed by tissue biopsy and treatment-naïve status for locally advanced or metastatic NSCLC(treatment for early-stage disease >12 months before randomization was permitted). Stable central nervous system(CNS) metastase patients were included after completing any definitive treatment/steroids for at least 2 weeks.
Lazertinib showed a significantly longer median PFS compared to gefitinib (20.6 vs 9.7 months; HR, 0.46; 95% [CI]: 0.34-0.63; P<0.001). The PFS benefit of lazertinib was consistent across predefined subgroups (Ex19del mutations: 20.8 vs 12.3 months; HR, 0.47; 95% CI: 0.31-0.71; P<0.001; L858R: 16.7 vs 9.6 months; HR, 0.44; 95% CI: 0.28-0.71; P=0.002; CNS metastases at study entry: 20.7 vs 9.5 months; HR, 0.33; 95% Cl: 0.18-0.58; P<0.001) including specific EGFR mutation types and CNS metastases at study entry.
ORR and disease control rates were not statistically different between the two treatments. Lazertinib demonstrated a longer median DoR compared to gefitinib (19.4 months [95% CI: 16.6-24.9] vs. 9.6 months [95% CI: 6.9-12.4]). Adverse event (AE) rates among Asian patients were consistent with the overall LASER301 population. AEs leading to discontinuation occurred in 13% for lazertinib and 12% for gefitinib.
Specific AEs included paronychia (24% vs. 25%), paresthesia (46% vs. 5%), increased alanine aminotransferase (13% vs. 33%), increased aspartate aminotransferase (11% vs. 29%), and pruritus (37% vs. 27%). The lazertinib group exhibited lower rates of rash (42% vs. 47%) and diarrhea (30% vs. 44%) compared to the gefitinib group.
The result demonstrated lazertinib’s efficacy advantage over gefitinib in Asian patients with EGFR-mutated NSCLC, maintaining comparable safety.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/2329
Clinical Trial: https://clinicaltrials.gov/study/NCT04248829
Reungwetwattana T, Cho BC, Lee KH, Pang YK, Fong CH, Kang JH, Lee YG, Lim CS, Danchaivijitr P, Lim YN, Lee Y, How SH, Geater S, Lee SS, Min YJ, Kim JH, Lee JS, Lee GW, Soo RA, Choi S, Lee SY, Ahn MJ. Lazertinib vs Gefitinib in Treatment-Naïve Patients with EGFR-mutated NSCLC: LASER301 Asian Subpopulation Analysis.
