Abstract 81P
Background
This is the first multicenter retrospective study to investigate the clinical outcomes of NSCLC patients with EGFR ex20ins mutations treated with furmonertinib in the real world. Besides, we explored related structural insights and kinase activity.
Methods
We performed a single-arm analysis of 37 patients to evaluate the efficacy and safety of furmonertinib. Meanwhile, we investigated the outcomes of furmonertinib versus osimertinib as a second-line treatment. In addition, the binding activities of different EGFR-TKIs to ex20ins were computationally predicted. We conducted a comparative analysis of the inhibition of cell viability and downstream alterations in kinase activity.
Results
Among 37 patients, the ORR was 67.6%(95%CI,50.2%-82.0%) and DCR was 94.6%(95%CI,81.8%-99.3%). All patients showed tumor shrinkage in target lesions (median-best-percent change, -35.58% [-74.78%, -1.49%]). Median PFS was 9.6 (95 % CI, 7.4-11.8) months, median DOR was 9.3 (95 % CI, 6.6-12.1) months, median OS was 15.7 (95% CI, 11.2-20.1) months. The most common events were vomiting or nausea (20 [54.0%]), increased ALT or AST (11 [29.7%]), anemia (11 [29.7%]), fatigue (9 [24.3%]), and low albuminemia (9 [24.3%]). Survival analysis showed that the ORR (64.3% vs. 12.5%, P=0.031) and median PFS (9.3 months vs 3.8 months, P=0.014) in the furmonertinib group (n=14) was better than osimertinib (n=8). Furthermore, based on the computational model findings, rather than erlotinib (GlideScore: -5.564; MM/GBSA: -52.8044), gefitinib (-7.68; -47.317), afatinib (-5.075; -44.64), mobocertinib (-7.213; -38.38) and sunvozertinib (-8.95; -57.03), furmonertinib (-11.085; -68.1575) and osimertinib (-10.031; -63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Following confirmation via cck8 assays, furmonertinib showed superior inhibitory effects across different ex20ins cell lines. In addition, several kinases(PKG1, PKAα, JAK1-b, and PKG2), exhibited significantly reduced kinase activity in Ba/F3 SVD cells treated with furmonertinib compared to osimertinib.
Conclusions
Advanced NSCLC patients with ex20ins mutation benefit from furmonertinib targeted therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-042), National Natural Science Foundation of China (82203978), National Natural Science Foundation of China (82073355), Kangmeng Charity Foundation (BJHA-CRP-059), Foundation of China Spark Program (XH-A047), Science Foundation of The Second Affiliated Hospital of Xi'an Medical College (24KY0118).
Disclosure
All authors have declared no conflicts of interest.