Abstract 685P
Background
Some small sample studies have reported the possible resistance mechanisms of post first-line (1L) osimertinib (osi) treatment failure. However, it is still urgent to explore the whole genomic profiles in these patients (pts) by paired tissue and plasma to guide subsequent treatment strategy to maximize pts clinical benefit.
Methods
EGFR mutant locally advanced or metastatic non-small cell lung cancer (NSCLC) pts after 1L osi treatment failure were enrolled. Genomic profiles of paired tissues and plasma samples at disease progression were analyzed using next-generation sequencing (NGS). Considering tissues as references, the sensitivity, specificity, and overall agreement of EGFR amplification (amp), MET amp, and EGFR C797S mutation in plasma samples were also analyzed.
Results
Between February 2022 and April 2024, 182 pts were enrolled. A total of 149 pts with paired tissue and plasma samples were analyzed. At disease progression, EGFR C797S mutation, other non-sensitive EGFR mutation, EGFR amp, MET amp, other amps, cell cycle gene alterations, fusion, and other mutations were detected in tissue samples. Similar genomic profile with different proportions were detected in paired plasma samples. Details were shown in the table. Taking the tissue sample results as references, the sensitivity, specificity, and overall agreement in plasma were 28.57%, 98.00%, 75.17% of EGFR amp, 15.22%, 95.15%, 70.47% of MET amp, 80.00%, 97.92%, 97.32% of EGFR C797S mutation, respectively. Four pts (2.7%) had histological transformation Table: 685P
Genomic profiles in tissue and plasma samples
| Alterations | Proportion in tissue (%) | Proportion in plasma (%) | |
| On-target | EGFR C797S mutation | 3.36 | 4.03 |
| Other non-sensitive EGFR mutation | 18.12 | 15.44 | |
| EGFR amp | 32.89 | 10.07 | |
| Off-target | MET amp | 30.87 | 7.38 |
| Other amps | 18.12 | 4.03 | |
| Cell cycle gene alterations | 33.56 | 3.36 | |
| Fusion | 7.38 | 10.07 | |
| Other mutations | 56.38 | 21.48 |
Conclusions
In this prospective study with the largest sample size, genomic profiles were consistent with previous studies in EGFR mutant locally advanced or metastatic NSCLC pts post 1L osi treatment failure. Plasma genotyping may be an alternative method to identify genomic profiles when tissues are not available.
Clinical trial identification
NCT05219162.
Editorial acknowledgement
Medical writing and editorial support were provided by Hangzhou Tigermed Consulting Co., Ltd.
Legal entity responsible for the study
AstraZeneca China.
Funding
AstraZeneca China.
Disclosure
All authors have declared no conflicts of interest.