VEGFR2 and CD34 expression associated with longer survival in patients with pleural mesothelioma in the IFCT-GFPC-0701 MAPS phase 3 trial.
Humans
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Endothelial Cells
Lung Neoplasms
/ drug therapy
Mesothelioma
/ drug therapy
Mesothelioma, Malignant
/ drug therapy
Pemetrexed
/ therapeutic use
Pleural Neoplasms
/ drug therapy
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
/ metabolism
Bevacizumab
CD34
Malignant pleural mesothelioma
Neo-angiogenesis
VEGFR2
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
15
03
2023
revised:
19
06
2023
accepted:
24
06
2023
medline:
23
10
2023
pubmed:
3
7
2023
entrez:
2
7
2023
Statut:
ppublish
Résumé
VEGF/VEGFR autocrine loop is a hallmark of pleural mesothelioma (PM). We thus assayed the prognostic and predictive values of VEGFR-2 [vascular endothelial growth factor receptor 2 or Flk-1] and CD34, a marker of endothelial cells, in samples from patients accrued in the Mesothelioma Avastin Cisplatin Pemetrexed Study ('MAPS', NCT00651456). VEGFR2 and CD34 expression were assayed using immunohistochemistry in 333 MAPS patients (74.3%), and their prognostic value was evaluated in terms of overall survival (OS) and progression-free survival (PFS) in univariate and multivariate analyses, before validation by bootstrap methodology. Positive VEGFR2 or CD34 staining was observed in 234/333 (70.2%) and 322/323 (99.6%) of tested specimens, respectively. VEGFR2 and CD34 staining correlated weakly, yet significantly, with each other (r = 0.36, p < 0.001). High VEGFR2 expression or high CD34 levels were associated with longer OS in PM patients in multivariate analysis (VEGFR2: adjusted [adj.] hazard ratio [HR]: 0.91, 95% confidence interval [CI] [0.88; 0.95], p < 0.001; CD34: adj. HR: 0.86, 95 %CI [0.76; 0.96], p = 0.010), with only high VEGFR2 expression resulting in significantly longer PFS (VEGFR2: adj. HR: 0.96, 95 %CI [0.92; 0.996], p = 0.032). Stability of these results was confirmed using bootstrap procedure. Nevertheless, VEGFR2 expression failed to specifically predict longer survival in bevacizumab-chemotherapy combination trial arm, regardless of whether the VEGFR2 score was combined or not with serum VEGF concentrations. VEGFR2 overexpression independently correlated with longer OS or PFS in PM patients, such biomarker deserving prospective evaluation as stratification variable in future clinical trials.
Identifiants
pubmed: 37393757
pii: S0169-5002(23)00825-5
doi: 10.1016/j.lungcan.2023.107287
pii:
doi:
Substances chimiques
Pemetrexed
04Q9AIZ7NO
Vascular Endothelial Growth Factor A
0
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
KDR protein, human
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT00651456']
Types de publication
Clinical Trial, Phase III
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107287Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Franck Morin reports financial support was provided by Roche-France (2013). Solenn Brosseau reports financial support was provided by CHU de Caen (APRI 2012). Gerard Zalcman reports financial support was provided by League against Cancer (2012). Guenaelle Levallet reports financial support was provided by Fond de Recherche en Santé Respiratoire (FRSR 2012).