British journal of cancer · 2026
Role of VEGFA/VEGFR2 signaling in predicting clinical outcomes of EGFR-TKI treatment in EGFR-mutant non-small cell lung cancer.
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Higashiyama Ryoko Inaba, Yoshida Tatsuya, Shiraishi Kouya, Miyakoshi Jun, Torasawa Masahiro, Shirasawa Masayuki, Masuda Ken, Shinno Yuki, Matsumoto Yuji, Okuma Yusuke, Yoshida Yukihiro, Goto Yasushi, Horinouchi Hidehito, Tuchida Takaaki, Hamamoto Ryuji, Yamamoto Noboru, Watanabe Shun-Ichi, Yatabe Yasushi, Kohno Takashi, Ohe Yuichiro
Аннотация
BACKGROUND: Dual 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.
METHODS: EGFR-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.
RESULTS: Among 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).
CONCLUSIONS: High VEGFA is associated with aggressive biology and inferior outcomes, correlating with shorter PFS for first/second-generation EGFR-TKIs but not for osimertinib.
METHODS: EGFR-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.
RESULTS: Among 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).
CONCLUSIONS: High VEGFA is associated with aggressive biology and inferior outcomes, correlating with shorter PFS for first/second-generation EGFR-TKIs but not for osimertinib.
Предметные рубрики MeSH
HumansCarcinoma, Non-Small-Cell LungVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor AErbB ReceptorsLung NeoplasmsFemaleMaleProtein Kinase InhibitorsRetrospective StudiesMutationAgedMiddle AgedIndolesSignal TransductionPyrimidinesAniline CompoundsPrognosisAcrylamidesAged, 80 and overAdult