ArticleBritish journal of cancer2026
Role of VEGFA/VEGFR2 signaling in predicting clinical outcomes of EGFR-TKI treatment in EGFR-mutant non-small cell lung cancer.
Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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20 authors.
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Abstract
backgroundDual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may improve outcomes in metastatic EGFR-mutant NSCLC, but VEGF inhibitors are not universally effective. We evaluated the impact of VEGFA and VEGFR2 expressions on EGFR-TKI outcomes.
methodsEGFR-mutant NSCLC patients from the National Cancer Center Hospital, were retrospectively analysed. The early-stage cohort comprised stage I-IIIA patients (1997-2019). The advanced-stage cohort included metastatic patients (2018-2022). VEGFA/VEGFR2 expressions were dichotomised by median transcripts per million.
resultsAmong 447 early-stage patients (median age 66), high VEGFA was associated with smoking, TP53 co-mutation, higher Brinkman Index, and higher tumour mutation burden (all p < 0.01). High VEGFA predicted shorter relapse-free survival (HR 2.10, 95% CI 1.63-2.71, p < 0.01) and overall survival (HR 2.07, 95% CI 1.46-2.95, p < 0.01). VEGFR2 expression showed no prognostic impact. In 146 relapsed patients receiving first-line EGFR-TKIs, high VEGFA was linked to shorter progression-free survival (PFS) overall (HR 1.70,95%CI 1.13-2.56, p = 0.009), particularly for first/second-generation EGFR-TKIs (HR 1.66,95%CI 1.08-2.54 p = 0.023), but not for osimertinib (p = 0.491). In 60 advanced-stage patients on osimertinib, PFS was unaffected by VEGFA (p = 0.102).
conclusionsHigh VEGFA is associated with aggressive biology and inferior outcomes, correlating with shorter PFS for first/second-generation EGFR-TKIs but not for osimertinib.
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