What question did this study set out to answer?

This study aims to evaluate the effectiveness of aumolertinib compared to other EGFR-TKIs in NSCLC patients with uncommon E19del mutations.

May 6, 2026Open Access

Aumolertinib in non-small cell lung cancer with uncommon EGFR exon 19 deletions: a real-world dual-center study

GYGuangjian YangShandong First Medical University LTL Z TianChinese Academy of Medical Sciences & Peking Union Medical College DHDongsheng HeShandong First Medical University

Key Points

This study aims to evaluate the effectiveness of aumolertinib compared to other EGFR-TKIs in NSCLC patients with uncommon E19del mutations.
Dual-center retrospective study including 118 patients with advanced/recurrent NSCLC and uncommon EGFR E19del mutations.
First-line treatment with second- and third-generation EGFR-TKIs, with molecular profiling via next-generation sequencing.
Analysis of progression-free survival across TKI subtypes and deletion categories.
Overall median progression-free survival was 15.5 months, with aumolertinib showing 15.9 months.
No significant difference in PFS between 2G and 3G TKIs (12.2 months vs 15.5 months; P = 0.19).
Aumolertinib demonstrated consistent efficacy across deletion subtypes, unlike osimertinib.

Abstract

BACKGROUND: Epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitors (TKIs) (EGFR-TKIs) show heterogeneous responses in patients with non-small cell lung cancer (NSCLC) harboring uncommon EGFR exon 19 deletion (E19del) mutations. This study evaluated the efficacy of second- and third-generation (2G/3G) EGFR-TKIs as first-line therapy in NSCLC patients with uncommon E19del variants. METHODS: This dual-center retrospective study included 118 patients with advanced or recurrent NSCLC harboring uncommon EGFR E19del mutations (excluding E746A750del). All patients received first-line treatment with 2G/3G EGFR-TKIs. Molecular profiling was performed using next-generation sequencing. Progression-free survival (PFS) was analyzed across TKI subtypes and deletion categories. Molecular modeling was performed to evaluate the drug-binding affinities. RESULTS: Among the 12 identified E19del subtypes, L747P753delinsS (21. 2%) and L747T751del (20. 3%) were predominant, with an overall median PFS (mPFS) of 15. 5 months. The differences in mPFS were observed across specific TKIs: aumolertinib (15. 9 months), osimertinib (15. 5 months), furmonertinib (15. 0 months) and afatinib (12. 2 months). No difference in PFS was observed between 2G (12. 2 months) and 3G TKIs (15. 5 months; P = 0. 19). The subgroup analysis revealed numerically shorter mPFS for T751-deletions (9. 4 months) compared to E746-deletions (15. 7 months) or L747-deletions (14. 8 months). Aumolertinib demonstrated consistent PFS regardless of deletion subtypes, whereas osimertinib-treated group exhibited subtype-dependent efficacy. Molecular modeling confirmed a stronger binding affinity of aumolertinib than osimertinib across prevalent L747-deletion variants. CONCLUSIONS: This comparative study demonstrated the improved and consistent activity of aumolertinib across diverse uncommon EGFR E19del subtypes compared to osimertinib, due to its enhanced binding affinity and structural adaptability. These findings support molecular subtype-guided TKI selection, aumolertinib as a first-line option for patients harboring uncommon EGFR E19del variants, particularly in settings lacking comprehensive molecular stratification.

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