ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2025
Identifying the genomic landscape of EGFR-mutant lung cancers with central nervous system metastases.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07551414 (A Prospective Study of Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy), which is not on this map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Prospective Study of Zorifertinib Plus Intra-Ommaya CSF Chemotherapy for Leptomeningeal Progression in NSCLC After Third-Generation EGFR-TKI Therapy
Who cites it
11 citing papers in PubMed.
- Central nervous system efficacy of third generationJournal of thoracic disease · 2026Article
- Delayed Occurrence of Lung Cancer Leptomeningeal Metastasis and Era-Associated Post-LM Survival: A 14-Year Single-Center Cohort Study.Thoracic cancer · 2026Article
- Review
- Risk Stratification and Strategies Towards Front-Line Therapy of EGFR-Mutant NSCLC: A Narrative Review.Cancers · 2026Review
- Single-cell and spatial transcriptomes reveal oligodendrocyte remodeling fatty acid metabolism microenvironment of lung cancer brain metastases.Journal of translational medicine · 2026Article
- Furmonertinib combined with bevacizumab in EGFR-TKI-resistant leptomeningeal metastasis: analysis of the CSF ctDNA molecular response and survival outcomes.British journal of cancer · 2026Article
- Advances in translational lung cancer research in 2025: a narrative review.Translational lung cancer research · 2026Review
- Lung-molGPA may stratify the prognostic impact of TP53 co-mutation in EGFR-mutant lung adenocarcinoma with brain metastases: a multi-center retrospective analysis.Therapeutic advances in medical oncology · 2026Article
- HER2 amplification as a resistance mechanism to osimertinib and its successful treatment with trastuzumab deruxtecan: a case report.Frontiers in oncology · 2026Article
- The evolving landscape of leptomeningeal metastases from NSCLC: an international, contemporary, multicenter cohort study.Annals of oncology : official journal of the European Society for Medical Oncology · 2026Article
- Clinical significance of HPV DNA and EGFR mutations in Egyptian NSCLC.Infectious agents and cancer · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
backgroundDespite the intracranial efficacy of osimertinib, central nervous system (CNS) metastases remain a major cause of morbidity and mortality in EGFR-mutant non-small-cell lung cancer (NSCLC). The genomic drivers of CNS dissemination are poorly understood. PATIENTS AND
methodsWe analyzed the clinicogenomic features of patients with EGFR-mutant NSCLC receiving first-line osimertinib with extracranial next generation sequencing (NGS) (n = 262) and individuals with intracranial NGS (n = 81). Paired extra- and intracranial NGS was available for 14 patients. Time-to-event analyses were conducted from time of metastatic diagnosis, except for time-to-treatment discontinuation (TTD), which began at treatment initiation.
resultsAmong 262 patients receiving first-line osimertinib, 53% developed CNS metastases (36% de novo, 16% acquired on treatment). The cumulative incidence of brain (BrM) and leptomeningeal metastases (LM) was 39% and 2% at 1 year, 49% and 6% at 3 years, and 54% and 12% at 5 years, respectively. CNS metastases correlated with a higher frequency of CARD11 amplifications (14% versus 3%, P = 0.031) and a lower frequency of MDM2 amplifications (1% versus 13%, P = 0.008) in extracranial NGS specimens, with otherwise similar genomic profiles. Patients who developed CNS metastases on treatment had worse overall survival (OS) [hazard ratio (HR) = 3.67, 95% confidence interval (CI) 2.41 to 5.59], followed by those with de novo (HR = 1.61, 95% CI 1.15 to 2.26), compared with those who never developed CNS metastases (P < 0.001). In multivariable Cox regression, atypical EGFR mutations were associated with shorter OS. Cell cycle pathway alterations were more frequent in BrM than LM samples (93% versus 47%, P = 0.003, q = 0.03). No other significant genomic differences were found between BrM and LM, or between paired CNS and systemic samples.
conclusionsPatients with atypical EGFR mutations or acquired CNS metastases on osimertinib have worse outcomes. Comparative NGS profiling of intra- and extracranial tumors suggest that CNS dissemination is driven by mechanisms beyond single-gene alterations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.