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Denize T, Farah S, Cimadamore A, et al. Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial. Clin Cancer Res. 2021;doi: 10.1158/1078-0432.CCR-21-3088.
Denize, T., Farah, S., Cimadamore, A., Flaifel, A., Walton, E., Sticco-Ivins, M. A., Labaki, C., Braun, D. A., Sun, M., Wang, E., Xie, W., Choueiri, T. K., & Signoretti, S. (2021). Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial. Clinical cancer research : an official journal of the American Association for Cancer Research, . https://doi.org/10.1158/1078-0432.CCR-21-3088
Denize, Thomas, et al. "Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial." Clinical cancer research : an official journal of the American Association for Cancer Research vol. (2021). doi: https://doi.org/10.1158/1078-0432.CCR-21-3088
Denize T, Farah S, Cimadamore A, Flaifel A, Walton E, Sticco-Ivins MA, Labaki C, Braun DA, Sun M, Wang E, Xie W, Choueiri TK, Signoretti S. Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial. Clin Cancer Res. 2021 Dec 17; doi: 10.1158/1078-0432.CCR-21-3088. Epub 2021 Dec 17. PMID: 34921022.
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Clin Cancer Res. 2021 Dec 17; doi: 10.1158/1078-0432.CCR-21-3088. Epub 2021 Dec 17.

Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial.

Clinical cancer research : an official journal of the American Association for Cancer Research

Thomas Denize, Subrina Farah, Alessia Cimadamore, Abdallah Flaifel, Emily Walton, Maura A Sticco-Ivins, Chris Labaki, David A Braun, Maxine Sun, Evelyn Wang, Wanling Xie, Toni K Choueiri, Sabina Signoretti

Affiliations

  1. Pathology, Brigham and Women's Hospital.
  2. Biostatistics and Computational Biology, Dana-Farber Cancer Institute.
  3. Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School.
  4. Medical Oncology, Dana-Farber Cancer Institute.
  5. Exelixis (United States).
  6. Department of Pathology, Brigham and Women's Hospital [email protected].

PMID: 34921022 DOI: 10.1158/1078-0432.CCR-21-3088

Abstract

PURPOSE: Anti-angiogenic 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.

EXPERIMENTAL DESIGN: 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).

RESULTS: 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 to everolimus, irrespective of MVD levels. Cabozantinib was also associated with improved ORR compared to 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.

CONCLUSIONS: High MVD and high MCD are associated with improved outcome in mccRCC but don't predict efficacy to cabozantinib versus everolimus. The high efficacy of cabozantinib in low angiogenic tumors allows us to speculate that its anti-tumor activity is not exclusively mediated by VEGFR inhibition.

Copyright ©2021, American Association for Cancer Research.

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