WCLC 2025 - Posters & ePosters-P3.12.37 First-Line Lazertinib With or Without Local Ablative Radiotherapy in Oligo-Metastatic EGFR-Mutant NSCLC

Pdf Summary

This multi-center, randomized phase II study (ABLATE, KCSG-LU21-11) evaluated the efficacy and safety of lazertinib, a third-generation EGFR tyrosine kinase inhibitor, with or without stereotactic body radiotherapy (SBRT) in patients with oligo-metastatic, EGFR-mutant non-small cell lung cancer (NSCLC). Lazertinib is known for its ability to penetrate the blood-brain barrier and has shown significant progression-free survival (PFS) benefits in treatment-naïve advanced EGFR-mutant NSCLC.<br /><br />The trial enrolled 67 patients from four South Korean centers between January 2022 and May 2023, randomized to receive lazertinib alone (n=34) or lazertinib plus SBRT (n=33). Inclusion criteria required patients to have 5 or fewer metastases across up to 3 organs, with all lesions suitable for SBRT. The primary endpoint was investigator-assessed PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety.<br /><br />At a median follow-up of 23 months, median PFS was 24.8 months for lazertinib monotherapy and 34.0 months with the addition of SBRT, indicating a clinically meaningful PFS improvement with combined therapy. OS data remain immature with few events. ORR was similar between groups (62% vs. 58%), and median DoR was comparable (~24-26 months). Progression patterns differed; most progression sites were original lesions in the monotherapy arm, while new sites predominated in the combination arm. Molecular profiling revealed frequent TP53 mutations.<br /><br />Safety profiles were manageable with no grade 3 or higher radiation pneumonitis and no grade 4 or 5 adverse events. Treatment discontinuation was low (3% with lazertinib alone, 6% with SBRT). The addition of SBRT was well tolerated and did not add significant toxicity.<br /><br />In conclusion, adding local ablative radiotherapy to lazertinib in oligo-metastatic EGFR-mutant NSCLC is feasible, safe, and may extend PFS compared to lazertinib alone, warranting further investigation.

Asset Subtitle

Jii Bum Lee

Meta Tag

Speaker Jii Bum Lee

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

lazertinib

EGFR-mutant non-small cell lung cancer

oligo-metastatic NSCLC

stereotactic body radiotherapy

phase II clinical trial

progression-free survival

third-generation EGFR tyrosine kinase inhibitor

TP53 mutation

treatment safety

combination therapy