Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
26
08
2021
revised:
03
11
2021
accepted:
13
12
2021
pubmed:
19
12
2021
medline:
8
4
2022
entrez:
18
12
2021
Statut:
ppublish
Résumé
Antiangiogenic VEGF receptor (VEGFR) inhibitors are approved for metastatic clear cell renal cell carcinoma (mccRCC) and their efficacy is higher in high angiogenic tumors. As cabozantinib inhibits multiple tyrosine kinase receptors, including VEGFRs, we tested whether markers of angiogenesis, including microvascular density (MVD) and mast cell density (MCD), could predict benefit from cabozantinib versus everolimus, using RCC samples from the METEOR (NCT01865747) trial. MVD and MCD were studied in 430 patients (cabozantinib = 216, everolimus = 214) by double immunohistochemistry for CD31 (vascular marker) and tryptase (mast cell marker) coupled with automated image analysis. Results from evaluable cases (MVD = 360, MCD = 325) were correlated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). MVD was positively correlated with MCD. In the whole cohort, high MVD and high MCD were associated with longer PFS; improved PFS was most evident in patients with high levels of both MCD and MVD. Cabozantinib was associated with improved PFS, OS, and ORR compared with everolimus, irrespective of MVD levels. Cabozantinib was also associated with improved ORR compared with everolimus, irrespective of MCD levels. For PFS and OS, the treatment effect for cabozantinib versus everolimus tended to be greater in tumors with low MCD. High MVD and high MCD are associated with improved outcome in mccRCC but do not predict efficacy to cabozantinib versus everolimus. The high efficacy of cabozantinib in low angiogenic tumors allows us to speculate that its antitumor activity is not exclusively mediated by VEGFR inhibition.
Identifiants
pubmed: 34921022
pii: 1078-0432.CCR-21-3088
doi: 10.1158/1078-0432.CCR-21-3088
pmc: PMC8866215
mid: NIHMS1766460
doi:
Substances chimiques
Anilides
0
Biomarkers
0
Pyridines
0
cabozantinib
1C39JW444G
Everolimus
9HW64Q8G6G
Banques de données
ClinicalTrials.gov
['NCT01865747']
Types de publication
Clinical Trial, Phase III
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
748-755Subventions
Organisme : NCI NIH HHS
ID : P50 CA101942
Pays : United States
Organisme : Exelixis Inc
ID : 5P30CA006516-56
Organisme : Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE
ID : P50-CA101942-12
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA238053
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA210068
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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