19P Resistance mechanism to first-line osimertinib in EGFR-mutated (EGFRm) advanced NSCLC (aNSCLC) in China: Preliminary data from FLOURISH study

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. 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. 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: 19PAcquired genetic resistance, n (%)Tissue (n=11)Plasma (n=17)Total (n=28)EGFR L718QND2 (11.8)2 (7.1)EGFR amp1 (9.1)ND1 (3.6)MET amp1 (9.1)1 (5.9)2 (7.1)FGFR mut2 (18.2)ND2 (7.1)HER2 amp1 (9.1)ND1 (3.6)BRAF mutND1 (5.9)1 (3.6)PIK3CA mutND1 (5.9)1 (3.6)ALK fusion1 (9.1)ND1 (3.6)CCND2 amp1 (9.1)ND1 (3.6)CCNE1 amp1 (9.1)ND1 (3.6)CDK6 amp1 (9.1)ND1 (3.6)Potential acquired genetic resistance, n (%)FANCM amp3 (27.3)ND3 (10.7)NKX2-1 amp3 (27.3)ND3 (10.7)ND, not detected Open table in a new tab ND, not detected 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.