Ameile (aumolertinib)

We present a patient with Anaplastic lymphoma kinase (ALK) fusion lung adenocarcinoma who received sequential treatment with ALK tyrosine kinase inhibitor (TKI) (crizotinib, PFS:32.3 months and then conteltinib, PFS: 29 months). Subsequently, the patient switched to third generation EGFR-TKI treatment with almonertinib. This case suggests EGFR mutation is one of the mechanisms of ALK-TKI resistance, highlights the value of re-biopsy in identifying potentially targetable resistance mechanisms and underscores the spatiotemporal heterogeneity of tumors under the selective pressure of ALK-TKI.

Based on the above results, the patient received chemotherapy with carboplatin and pemetrexed disodium combined with targeted therapy using the EGFR tyrosine kinase inhibitor (TKI) almonertinib mesylate tablets. The two cases reported in this paper demonstrate that targeted and immune treatment plans based on the tissue of origin of the tumor can serve as a clinical option for patients with CUP. These findings may provide new information and references for clinical decision-making in the management of CUP.

Overall survival data were immature (data maturity, 4%). The ACROSS2 trial provides the first prospective evidence supporting a genotype-directed, chemotherapy-targeted intensification approach favoring aumolertinib plus carboplatin-pemetrexed for this molecularly defined population.

In vitro experiments using PC-9 cells included Cell Counting Kit-8 (CCK-8) assays (cell viability), wound healing assays (migration), flow cytometry (apoptosis/cell cycle), RNA sequencing (RNA-seq), public transcriptome datasets (GSE193258, GSE178975) were analyzed to compare ETS variant transcription factor 4 (ETV4) expression across EGFR-TKIs (aumolertinib, osimertinib, and gefitinib). ETV4 knockdown enhanced aumolertinib-induced apoptosis/G2/M arrest in vitro and synergistically suppressed tumor growth in vivo. These findings revealed that ETV4 enhanced the therapeutic efficacy of aumolertinib in vitro and in vivo, indicating that ETV4 is a potential therapeutic co-target, serving as a treatment strategy to prevent the acquired resistance induced by aumolertinib.

The rapid progression suggests that this specific germ-line variant may confer inherent TKI resistance, potentially exacerbated by the presence of a concurrent KRAS G12V mutation and drug-drug interactions between almonertinib and antituberculosis medications. It underscores the clinical challenge of germ-line EGFR mutations and emphasizes the need for further research to establish effective therapeutic strategies for such rare genotypes.

Since 1997, EGFR tyrosine kinase inhibitors (EGFR-TKIs) have evolved from first-generation agents, such as gefitinib, erlotinib, and icotinib, to second-generation agents like afatinib and dacomitinib, now to third-generation agents, including osimertinib, aumolertinib, furmonertinib, befotertinib, rezivertinib, rilertinib, limertinib, lazertinib, mifanertinib for EGFR L858R, sunvozertinib for EGFR exon 20 insertion (20ins), and zorifertinib for EGFR-sensitive mutation with brain metastases. Over the past 30 years, substantial advancements have been made in the comprehensive management of EGFR-mutant NSCLC. This systemic review provides the history of the development of EGFR-TKI therapy for NSCLC from 1997 to 2026, highlighting clinical milestones, emerging therapies, and future directions in this rapidly evolving field.

The combination of aumolertinib and icotinib shows encouraging efficacy and a tolerable safety profile in patients with EGFR-mutant NSCLC and BMs, supporting its potential as a therapeutic option warranting further investigation.

Exploratory analysis revealed that PFS benefits from aumolertinib plus apatinib predominantly in those with TP53 mutations. As an infusion-free option, aumolertinib plus apatinib demonstrated PFS benefits with manageable safety in patients with untreated, EGFR-mutant, advanced NSCLC.

The patient showed no meaningful response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including the first-generation (Icotinib), the second-generation (Afatinib) and the third-generation (Aumolertinib). Trophoblast cell surface antigen 2-antibody-drug conjugate (TROP2-ADC) and immune checkpoint inhibitors (ICIs) combined with Bevacizumab also resulted in limited efficacy. Based on the clinical features and treatment response of this case, we reviewed the published literature about the pathological characteristics, mutational landscape, and current therapeutic approaches for PEAC, with a particular focus on the therapeutic challenges and future research directions for EGFR-mutant PEAC, aiming to provide insights for clinical practice and further studies..

P=N/A, N=51, Not yet recruiting, Tianjin Chest Hospital; Tianjin Chest Hospital

P=N/A, N=66, Not yet recruiting, Beijing hospital; Beijing hospital

P=N/A, N=30, Not yet recruiting, The First Affiliated Hospital of Zhengzhou University; The First Affiliated Hospital of Zhengzhou University