Abstract 19P
Background
Osimertinib is the preferred first-line treatment for patients (pts) with EGFRm aNSCLC. However, most pts treated with osimertinib will develop resistance. We present the preliminary resistance mechanism results from FLOURISH study.
Methods
FLOURISH was a multi-center, prospective, non-interventional study to investigate the incidence of resistance among pts on osimertinib as first-line treatment for EGFRm aNSCLC (NCT04391283). 473 eligible pts were recruited from 22 sites from Jul 27, 2020 to Apr 27, 2022. Here included 68 pts who progressed after osimertinib and performed next-generation sequencing. 28 pts had paired pre-treatment samples.
Results
The data cut-off date was Dec 4, 2023. Among the 68 pts, 45.6% (31) had detected genetic resistance after progression, including 29.4% (20) were off-target (EGFR-independent), 10.3% (7) were on-target (EGFR-dependent) and 5.9% (4) were both. MET amplification (amp) 8.8% (6), EGFR amp 7.4% (5), and EGFR L718Q 7.4% (5) were the most prevalent resistance, followed by PIK3CA mutation (mut) 5.9% (4) and FGFR mut 5.9% (4), C797S 4.4% (3) and MET 14 deletion (del) 1.5% (1). Of the 28 paired pts, 39.3% (11) were 19 del and 60.7% (17) were 21 L858R, 92.9% (26) were adenocarcinoma, 60.7% (17) were paired plasma and 39.3% (11) were paired tissue. 39.3% (11) had acquired genetic resistance, with 28.6% (8) were off-target and 10.7% (3) were on-target (Table). Table: 19P
| Acquired genetic resistance, n (%) | Tissue (n=11) | Plasma (n=17) | Total (n=28) |
| EGFR L718Q | ND | 2 (11.8) | 2 (7.1) |
| EGFR amp | 1 (9.1) | ND | 1 (3.6) |
| MET amp | 1 (9.1) | 1 (5.9) | 2 (7.1) |
| FGFR mut | 2 (18.2) | ND | 2 (7.1) |
| HER2 amp | 1 (9.1) | ND | 1 (3.6) |
| BRAF mut | ND | 1 (5.9) | 1 (3.6) |
| PIK3CA mut | ND | 1 (5.9) | 1 (3.6) |
| ALK fusion | 1 (9.1) | ND | 1 (3.6) |
| CCND2 amp | 1 (9.1) | ND | 1 (3.6) |
| CCNE1 amp | 1 (9.1) | ND | 1 (3.6) |
| CDK6 amp | 1 (9.1) | ND | 1 (3.6) |
| Potential acquired genetic resistance, n (%) | |||
| FANCM amp | 3 (27.3) | ND | 3 (10.7) |
| NKX2-1 amp | 3 (27.3) | ND | 3 (10.7) |
ND, not detected
Conclusions
The acquired genetic resistance rate to first-line osimertinib in FLOURISH study was consistence with previous data, and in which MET amp, FGFR mut and EGFR L718Q were common acquired resistance mechanisms among paired pts.
Clinical trial identification
NCT04391283.
Legal entity responsible for the study
Guangdong Association of Clinical Trials.
Funding
AstraZeneca China.
Disclosure
All authors have declared no conflicts of interest.