EGFR exon 19 deletion

This study demonstrates that EGFR-targeted therapy, when used in a first-line setting, significantly improves OS and PFS in this population. Further research is warranted to optimise treatment strategies, particularly in resource-limited settings.

P2, N=150, Active, not recruiting, Myung-Ju Ahn | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

Aumolertinib plus anlotinib was effective and well-tolerated as first-line therapy in EGFR-mutant NSCLC patients with BMs. Trial Registration: ClinicalTrials.gov(identifier NCT04978753, registered July 20, 2021).

A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

Furthermore, evaluation of 7c in HCC827 (exon 19 deletion) mutation, which is a cell model highly sensitive to tyrosine kinase inhibitors, showed that the tested compound exhibited lower inhibition than erlotinib...Furthermore, 7c caused an increase in the levels of caspase 3 (4.68 folds) and caspase 9 (4.54 folds) in HCT-116 cells. Additionally, in silico studies of 7c showed a plausible binding mode that correlates with its potent inhibitory activity against the two enzymes, whereas ADME prediction revealed a favorable oral absorption.

Both almonertinib and osimertinib demonstrated good efficacy in patients with brain metastases, and PD-L1 expression was not associated with the prognosis of EGFR L858R mutant NSCLC. Finally, no significant difference between osimertinib and almonertinib for the treatment of patients with EGFR L858R mutations was observed. Both options remain viable for these patients.

Molecular events included the emergence of a BRAF V600E mutation responsive to dabrafenib plus trametinib and the acquisition of an EGFR exon 19 deletion responsive to Osimertinib. EVA/PCD identified activity for targeted agents and revealed synergy for vinorelbine plus Osimertinib not predicted by genomic profiling, which provided additional response. This case highlights clonal evolution in NSCLC and illustrates how serial tissue analyses correlating phenotypic and genomic events can offer therapeutic interventions to provide long-term survival. The integration of functional and genomic profiling may improve personalized treatment in NSCLC by interrogating tumor heterogeneity and clonal evolution to inform rational therapeutic selection.

The patient achieved prolonged disease-free survival following comprehensive treatment, including surgical resection, chemotherapy, EGFR-tyrosine kinase inhibitor (TKI) therapy, and endocrine therapy. This case highlights the importance of molecular profiling in guiding personalized therapeutic strategies for TTM, particularly when actionable mutations are present.

Patients received RAM (10 mg/kg every 2 wk) plus GEF (250 mg once daily) until disease progression (period 1); patients with disease progression who acquired a T790M mutation received RAM plus osimertinib (80 mg once daily) (period 2). Treatment-emergent T790M rate post progression was 81.3%. RELAY+ revealed a favorable benefit-risk profile for RAM plus GEF in East Asian patients with untreated EGFR-mutated metastatic NSCLC, supporting RAM plus GEF as an alternative first-line treatment option, particularly in those with an L858R mutation.

The study identified multiple genomic characteristics associated with primary and secondary resistance to first-line afatinib treatment in EGFR- and ERBB2-positive subpopulations.

In the ITT population, we found no differences in OS between amivantamab-lazertinib and osimertinib-chemotherapy, despite a slightly higher PFS of the latter. Osimertinib-chemotherapy could be more effective in patients with CNS metastases, without liver metastases, and EGFR L858R mutation, however we could not compare OS in these subgroups. Due to the indirect nature of the comparison and the limitation of the methods our results are not definitive, but rather hypothesis-generating. Other factors must be considered in the choice of the treatment, including patient's characteristics, the safety profile of the combinations, and center's facilities and expertise.