A phase 2 clinical trial led by Korean investigators demonstrated that combining the third-generation EGFR inhibitor lazertinib (Leclaza® in Korea, Lazcluzy® internationally) with stereotactic body radiotherapy (SBRT) significantly prolonged progression-free survival (PFS) compared with lazertinib alone in patients with EGFR-mutant oligometastatic non-small cell lung cancer (NSCLC).
The multicenter, randomized study enrolled 67 patients with EGFR exon 19 deletion (Ex19del) or L858R mutations across four Korean institutions: Yonsei Cancer Center, Asan Medical Center, Haeundae Paik Hospital, and Gachon University Gil Medical Center. Patients were randomly assigned to lazertinib monotherapy (240 mg daily, n=34) or lazertinib plus SBRT (n=33). The primary endpoint was PFS, with secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response (DoR), and safety.
At a median follow-up of 23 months, the median PFS was 24.8 months for monotherapy versus 34.0 months for the combination-an improvement of nearly 9 months. Subgroup analyses showed that patients with Ex19del mutations in the combination arm had not yet reached median PFS, compared with 24.8 months in the monotherapy arm. For L858R mutations, median PFS was 27.6 months with the combination versus 20.3 months with monotherapy. OS data were immature, with only three deaths reported, and ORR was similar between groups (62% vs. 58%). Disease progression patterns differed: most recurrences in the monotherapy group occurred at existing lesions, while in the combination group, 92% of progressions were due to new lesions.
Safety was favorable. No new treatment-related toxicities emerged with the combination, no grade ≥3 radiation-induced pneumonitis was reported, and neither group experienced grade 4 adverse events. Investigators highlighted that the lazertinib–SBRT combination improved PFS without compromising safety. Ongoing translational analyses using whole-exome and bulk RNA sequencing aim to identify potential acquired resistance mechanisms under the combination strategy.
The study concluded that lazertinib plus SBRT is a feasible and clinically meaningful treatment approach for patients with EGFR-mutant oligometastatic NSCLC, with larger trials needed to determine its potential as a new first-line standard of care.
Background:
Lazertinib, developed by Korea’s Yuhan Corporation, is a third-generation EGFR tyrosine kinase inhibitor (TKI) with strong blood–brain barrier penetration. It was licensed to Johnson & Johnson in 2018 and has shown efficacy both as monotherapy and in combination with amivantamab (Rybrevant®).
Stereotactic body radiotherapy (SBRT) is an advanced form of external beam radiation therapy that delivers highly focused, high-dose radiation to tumor sites with sub-millimeter precision. By minimizing exposure to surrounding healthy tissues, SBRT enables effective local tumor control while reducing treatment-related toxicity.
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