Abstract 691P
Background
Osimertinib (Osi) is as preferred 1L treatment regimen for EGFRm advanced NSCLC. However, the drug resistance is inevitable. FLOURISH is a real-world, multi-center, prospective study of 1L Osi in Chinese patients(pts) with EGFRm advanced NSCLC. Here, we reported acquired resistance mechanisms to 1L Osi from this study.
Methods
Pts with untreated EGFRm advanced NSCLC and received Osi as 1L were prospectively enrolled. Paired tissue and plasma samples were collected at baseline (before first dose of osimertinib) and at disease progression (PD). Next generation sequencing (NGS) was performed. The resistance mechanism was analyzed.
Results
In this study, a total of 481 pts were eligible and received at least one dose of Osi. At the time of data cutoff (April 27, 2024), 185 pts had PD. Of these, 35 pts (18.8%) had evaluable paired biopsies at baseline and PD, 19 pts and 16 pts have paired tissue and plasma samples, respectively. Key genetic alterations included acquired on-target resistance occurred in 11.4% pts, including EGFR amplification (amp) (5.7%) and EGFR L718Q (5.7%). MET amp (11.4%) was still the most frequent acquired off-target resistance, followed by FGFR mutations (5.7%). Some other genomic alterations which may lead to acquired resistance, such as NKX2-1 amp (14.3%) and FANCM amp (8.6%) were also detected. ND, not detected; amp, amplification; mut, mutations.
Conclusions
The acquired resistance mechanism to 1L Osi in this study is consistent with previous data and MET amp is still as one of the main mechanisms. FANCM amp was identified as a potential new resistance marker. The resistance mechanism detection in plasma is limited, especially for gene amp.
Clinical trial identification
NCT04391283.
Editorial acknowledgement
Legal entity responsible for the study
Guangdong Association of Clinical Trials, GACT.
Funding
AstraZeneca China.
Disclosure
All authors have declared no conflicts of interest.