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4ms
Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with NSCLC Harboring EGFR Exon 19 Insertions: A Report from the LC-SCRUM-Asia (IASLC-WCLC 2024)
We also studied preclinical Ba/F3 models expressing EGFR -K745_E746insIPVAIK (Ba/F3-IPVAIK) and EGFR -delE746_A750 (Ba/F3-Del19) to investigate the sensitivity to 1st-generation (gen) (gefitinib and erlotinib), 2nd-gen (afatinib, dacomitinib, and poziotinib), 3rd-gen (osimertinib), and EGFR exon 20 insertion active TKIs (mobocertinib, sunvozertinib, and zipalertinib). The preclinical therapeutic window of Ba/F3-IPVAIK and Ba/F3-Del19 for all the 2nd generation TKIs were similarly favorable, whereas Ba/F3-IPVAIK had much unfavorable therapeutic windows to other EGFR-TKIs compared to Ba/F3-Del19. Conclusions : Our clinical and preclinical findings indicate 2nd-gen EGFR-TKIs are more effective than 1st and 3rd-gen EGFR-TKIs in patients with EGFR exon 19 insertions.
Clinical
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR (Fibroblast Growth Factor Receptor) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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TP53 mutation • EGFR mutation • PIK3CA mutation • EGFR amplification • EGFR exon 20 insertion • EGFR expression • FGFR mutation • EGFR exon 20 mutation • EGFR K745_E746insIPVAIK • EGFR mutation + PIK3CA mutation • EGFR exon 19 insertion • EGFR E746
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Oncomine Precision Assay
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Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Vizimpro (dacomitinib) • Pozenveo (poziotinib) • Exkivity (mobocertinib) • sunvozertinib (DZD9008) • zipalertinib (CLN-081)