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Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset
Ross A Soo1, Byoung Chul Cho2, Joo-Hang Kim3
1Department of Haematology-Oncology, National University Cancer Institute, Singapore.
Introduction:
Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases.
Methods:
Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response.
Results:
Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population.
Conclusions:
In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.
Insights
Lazertinib significantly improved intracranial progression-free survival in patients with EGFR-mutated NSCLC and brain metastases compared to gefitinib. This third-generation EGFR inhibitor demonstrated more durable responses in the central nervous system.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Non-small cell lung cancer (NSCLC) with EGFR mutations often develops brain metastases.
- Targeted therapies like EGFR tyrosine kinase inhibitors (TKIs) are standard treatments.
- Efficacy of TKIs in patients with central nervous system (CNS) metastases requires specific evaluation.
Purpose of the Study:
- To evaluate the efficacy of lazertinib versus gefitinib in patients with EGFR-mutated advanced NSCLC and baseline CNS metastases.
- To compare intracranial progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).
Main Methods:
- Phase 3, randomized, one-to-one trial (LASER301) comparing lazertinib and gefitinib.
- Inclusion of treatment-naive patients with EGFR-mutated NSCLC and asymptomatic or stable CNS metastases.
- Centralized, blinded assessment of intracranial endpoints using RECIST v1.1 criteria.
Main Results:
- 86 patients had baseline CNS metastases (45 lazertinib, 41 gefitinib).
- Median intracranial PFS was significantly longer with lazertinib (28.2 months) vs. gefitinib (8.4 months) (HR=0.42, p=0.02).
- Intracranial ORR was numerically higher with lazertinib (94%) vs. gefitinib (73%), with longer median DOR for lazertinib.
Conclusions:
- Lazertinib significantly improves intracranial PFS in patients with EGFR-mutated NSCLC and CNS metastases.
- Lazertinib offers more durable intracranial responses compared to gefitinib.
- These findings support lazertinib as a preferred treatment option for this patient population.
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