20P Genomic profiles in EGFR mutant locally advanced or metastatic NSCLC patients post osimertinib first line treatment failure: An interim analysis of GPS study

Osimertinib represents the current standard treatment for advanced EGFR-mutated NSCLC in the first-line (1L) setting. Acquired resistance inevitably occurs. The exploration of genomic profiles in resistant patients (pts) is vital. EGFR mutant locally advanced or metastatic NSCLC pts post osimertinib 1L treatment failure were prospectively enrolled. Genomic profiles of paired tissues and plasma samples at progression were analyzed using NGS. Considering tissues as references, the sensitivity and specificity of EGFR amplification (amp), MET amp, EGFR C797S mutation and other non-sensitive EGFR mutations in plasma samples were analyzed. From Feb 2022 to Oct 2023, 86 pts were analyzed with paired tissue and plasma samples. The median age was 63 years (range, 33-84 years), and 45.3% were males. The majority had ECOG PS 0-1 (97.7%). At progression, EGFR C797S mutation (3.5%), other non-sensitive EGFR mutation (15.1%), EGFR amp (30.2%), MET amp (27.9%), other amps (16.3%), cell cycle gene alterations (25.6%), fusion (11.6%) and other mutations (20.9%) in tissue samples were detected. Two pts (2.3%) had histological transformation, one experienced SCLC transformation, the other one experienced squamous carcinoma transformation. Same genomic profile with different proportions were detected in paired plasma samples, including EGFR C797S mutation (4.7%), other non-sensitive EGFR mutation (17.4%), EGFR amp (10.5%), MET amp (8.1%), other amps (7.0%), cell cycle gene alterations (4.7%), fusion (14.0%) and other mutations (11.6%). Using tissues as references, the sensitivity of EGFR amp, MET amp, EGFR C797S mutation and other non-sensitive EGFR mutation were 34.62%, 16.67%, 66.67% and 76.92%, respectively in paired plasma samples. The specificity were 100.00%, 95.16%, 97.59% and 93.15%, respectively in paired plasma samples. Genomic profiles were complicated in EGFR mutant locally advanced or metastatic NSCLC pts post osimertinib 1L treatment failure, with the most common being EGFR amp and MET amp. Plasma genotyping is an alternative method to identify resistance profiles when tissues are not available.