EGFR L858R

He received afatinib as frontline treatment and showed a partial response; however, the right lung lesion progressed after 14 months of treatment...Because EGFR testing using resected tissue showed only the original mutation, we switched his regimen to pemetrexed and carboplatin...Although an association between MET amplification and rapidly progressive lung cancer has been predicted previously, to the best of our knowledge, this is the first report on the potential contribution of other mutations, such as those in RNA-binding motif 10, during MET-driven rapid progression. Our report highlights the importance of more active utilization of molecular profiling for the emergence of resistance during tyrosine kinase inhibitor use and the early identification of MET amplification and timely initiation of MET-targeted therapy, such as MET inhibitors in combination with EGFR-TKIs, to potentially mitigate rapid disease progression and clinical deterioration.

P3, N=605, Active, not recruiting, Daiichi Sankyo | Trial completion date: Jan 2026 --> Feb 2027

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.

Among the tested compounds, Tetrandrine, Dauricine, and Olmutinib exhibited robust binding affinities across both wild-type and mutant EGFR configurations, highlighting their potential as effective inhibitors. The integrated approach of combining molecular docking using CB-dock2, ADMET profiling, and Lipinski's rule of five provides a robust framework for preliminary drug candidate screening, potentially accelerating the development of more precise and effective EGFR-targeted therapies. The findings contribute to the growing body of research exploring alternative and more nuanced strategies for inhibiting EGFR-driven oncogenic mechanisms, highlighting the importance of computational methods in identifying novel molecular targets with improved specificity and reduced side effects.

P2, N=23, Recruiting, Taipei Veterans General Hospital, Taiwan | Not yet recruiting --> Recruiting | Trial completion date: Jun 2027 --> Dec 2027 | Trial primary completion date: Jun 2026 --> Dec 2026

P=N/A, N=300, Active, not recruiting, Fudan University

P2/3, N=854, Recruiting, AbbVie | Trial completion date: Dec 2031 --> Nov 2036 | Trial primary completion date: Dec 2031 --> Nov 2036

P1/2, N=14, Not yet recruiting, Academisch Ziekenhuis Maastricht

P1/2, N=53, Not yet recruiting, Shanxi Province Cancer Hospital

The developed ESR-Net demonstrates promising potential for early detection of EGFR mutations and subtypes with multicenter data, which may promote optimal treatment management for patients with brain metastatic NSCLC.

P2, N=63, Not yet recruiting, Jiangmen Central Hospital

First-line treatment with the tyrosine kinase inhibitor afatinib was associated with improved OS compared with that of patients treated with erotinib or gefitinib. In addition, combination therapy with the angiogenesis inhibitor bevacizumab had a positive impact on OS...These findings highlight the importance of molecular profiling and individualized treatment strategies in optimizing OS for patients with advanced lung adenocarcinoma. Furthermore, the validated machine learning models may serve as useful tools for risk stratification and personalized prognostic assessment to support clinical decision-making.