Abstract 140P
Background
The 3rd generation EGFR-TKIs for early operable NSCLC patients are being explored in neoadjuvant setting to reduce relapse rates. However, tissue biopsy is a critical limitation for detecting early-stage EGFR mutant cases before surgery. Previous studies have demonstrated that exosome-based bronchoalveolar lavage fluid (BALF) liquid biopsy (ExoBAL) provides greater than 95% sensitivity, specificity, and concordance rates when compared to tissue biopsy for EGFR genotyping in advanced NSCLC. This study aims to evaluate the performance of ExoBAL in detecting EGFR mutations, as well as therapeutic response of neoadjuvant lazertinib treatment and surgical outcomes.
Methods
This prospective, single-arm, phase II study (NCT 05469022) enrolled patients with ExoBAL-confirmed sensitive EGFR mutations, even without tissue biopsy. Participants received neoadjuvant lazertinib for 9 weeks, followed by restaging and surgery. Adjuvant lazertinib was given for 3 years to patients with pathological stage II or higher. The primary endpoint was the objective response rate (ORR). Secondary endpoints included EGFR concordance rates between ExoBAL and surgical tissue, downstaging rates, and major pathological response (MPR, defined as ≤10% viable malignant cells).
Results
Among 128 patients screened, 48 cases of EGFR mutation were detected, of whom 40 patients were enrolled to receive neoadjuvant lazertinib therapy for 9 weeks. Finally, 34 patients completed the neoadjuvant treatment and surgery. The ORR was 67.6% and there was no disease progression. The surgical histology of 34 patients revealed 33 adenocarcinomas and 1 adenosquamous carcinoma. R0 resection rate was 97.1% with only 1 case of R1 resection, which received adjuvant lazertinib therapy. Overall downstaging rate was 55.8 %. MPR was observed in 18.2% of cases (6 out of 34). The concordance rate of EGFR genotyping between surgical tissue and ExoBAL was 97.0% (33/34).
Conclusions
This study demonstrated that ExoBAL can detect resectable EGFR-mutant NSCLC prior surgery without tissue biopsy. ExoBAL is a promising method for broadening the use of neoadjuvant EGFR-TKIs in resectable EGFR-mutant NSCLC patients.
Legal entity responsible for the study
The authors.
Funding
Yuhan Corporation.
Disclosure
All authors have declared no conflicts of interest.