Bronchoalveolar lavage fluid cfDNA liquid biopsy-guided neoadjuvant lazertinib in resectable EGFR-mutant non-small cell lung cancer: a prospective phase II study
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Background: Reliable preoperative molecular testing is increasingly important in resectable non-small cell lung cancer (NSCLC), particularly when tissue biopsy is not feasible or yields insufficient material. We evaluated the feasibility of bronchoalveolar lavage fluid cell-free DNA liquid biopsy (BALiquid) as a preoperative epidermal growth factor receptor (EGFR) genotyping platform and assessed the clinical efficacy of neoadjuvant lazertinib in patients with potentially resectable EGFR-mutant NSCLC. Methods: A total of 128 patients with computed tomography (CT) findings suggestive of potentially resectable lung cancer underwent bronchoscopy with bronchoalveolar lavage near the target lesion. EGFR genotyping was performed using polymerase chain reaction (PCR)-based BALF cfDNA analysis. Patients with sensitizing EGFR mutations detected by BALiquid received neoadjuvant lazertinib for 9 weeks followed by surgical resection. Diagnostic performance, radiologic response, surgical outcomes, pathologic response, and safety were evaluated. Results: Among 48 patients with BALiquid-detected EGFR mutations, 40 were enrolled and 34 completed neoadjuvant lazertinib followed by surgery. BALiquid EGFR genotyping demonstrated a sensitivity of 74%, a specificity of 97.0%, a positive predictive value of 97.4%, a negative predictive value of 71.7% and 83.3% of concordance rate compared with surgical tissue genotyping. The all-treated objective response rate (ORR) was 57.5% [23/40; 95% confidence interval (CI): 40.9-73.0%], and the ORR in the per-protocol population was 67.6% (23/34; 95% CI: 49.5-82.6%). R0 resection was achieved in 33 of 34 patients. Pathologic downstaging occurred in 55.9% of patients, and major pathologic response was achieved in 6 of 34 patients (17.6%). Grade 3 or higher treatment-related adverse events occurred in 4/40 patients (10.0%). Conclusions: BALiquid may serve as a complemental preoperative EGFR genotyping approach to provide genetic information when tissue is unavailable or insufficient. BALiquid-guided neoadjuvant lazertinib demonstrated meaningful antitumor activity, favorable surgical outcomes, and an acceptable safety profile in patients with potentially resectable EGFR-mutant NSCLC.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223979964