872P - Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib (C) vs everolimus (E) in advanced renal cell carcinoma (RCC)

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Renal Cell Cancer
Genitourinary Cancers
Translational Research
Presenter Thomas Powles
Citation Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371
Authors T. Powles1, R.J. Motzer2, D.J. George3, E. Jonasch4, S. Pal5, N.M. Tannir6, S. Signoretti7, T.H. Mai8, C. Scheffold9, E. Wang10, D.T. Aftab11, B. Escudier12, T.K. Choueiri13
  • 1Centre For Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ - London/GB
  • 2Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 3Duke Cancer Institute, Duke University Medical Center, 27710 - Durham/US
  • 4Department Of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 5Department Of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte/US
  • 6Department Of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston/US
  • 7Pathology, Brigham and Women’s Hospital, Boston/US
  • 8Pharmacometrics, Ann Arbor Pharmacometrics Groups, Ann Arbor/US
  • 9Clinical Development, Exelixis, Inc, South San Francisco/US
  • 10Translational Medicine, Exelixis, Inc, South San Francisco/US
  • 11Executive Administration, Exelixis, Inc., 94080 - South San Francisco/US
  • 12Medical Oncology, Gustave-Roussy, 94800 - Villejuif  /FR
  • 13Lank Center For Genitourinary Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US

Abstract

Background

C inhibits tyrosine kinases that promote oncogenesis and resistance to antiangiogenic therapy in RCC, including MET, AXL, and VEGF receptors. In the phase 3 METEOR trial (NCT01865747), C significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs E in patients (pts) with advanced RCC after prior VEGFR-targeted therapy (Choueiri, Lancet Oncol 2016). The current study evaluated outcomes based on plasma biomarker levels.

Methods

Plasma samples collected at baseline and during treatment from 621 of 658 randomized pts were analyzed for HGF, MET, Gas6, AXL, VEGF, VEGFR2, CA9, and IL-8 by ELISA (Assay Gate, Ijamsville, MD). PFS and OS were analyzed based on low vs high (< median vs ≥ median) biomarker levels at baseline.

Results

Analyses of PFS and OS based on baseline biomarker levels showed improvement with C vs E (hazard ratio

Conclusions

PFS and OS improved with C irrespective of baseline plasma biomarker levels in previously treated pts with advanced RCC vs E. However, low baseline levels of a subset of biomarkers were associated with better clinical outcomes with C.

Clinical trial identification

NCT01865747

Legal entity responsible for the study

Exelixis, Inc.

Funding

Exelixis, Inc.

Disclosure

T. Powles: Consultant/advisory: Exelexis Novartis GSK; Research funding: Exelexis Novartis GSK Genetech. R.J. Motzer: Consulting Role: Exelixis, Eisai, Pfizer, Novartis; Research Funding (institution): Exelixis, Eisai, Bristol-Myers Squib, Pfizer, Novartis. D.J. George: Ad Board: Bristol-Myers Squib, Exelixis, Genentech/Roche, Novartis, Pfizer; Corporate-sponsored Research: Bristol-Myers Squib, Exelixis, Genentech/Roche, Novartis, Pfizer Other: Acceleron – IDMC. E. Jonasch: Research funding: Exelixis, Pfizer, Novartis; Honoraria: Bristol-Myers Squib, Eisai, Exelixis, Novartis, Pfizer. S. Pal: Honoraria: Novartis, Medivation and Astellas Pharma; Consulting fees: Pfizer, Novartis, Aveo, Genentech, Exelixis, Bristol-Myers Squib, Astellas and GSK. N.M. Tannir: Ad Board: Bristol-Myers Squib, Exelixis, Nektar, Novartis, Pfizer, Argos, Calithera; Corproate-sponsored Research: Bristol-Myers Squib, Exelixis, Epizyme, Novartis, Miranti. S. Signoretti: Consulting Role: AstraZeneca, Merck; Research Funding (institution): AstraZeneca, Exelixis Patents/Intellectual Property: Biogenex. C. Scheffold: Employee: Exelixis. E. Wang, D.T. Aftab: Employee: Exelixis, Inc. B. Escudier: Honorarium: Bristol-Myers Squib, Novartis, Pfizer, Ipsen, Roche, Bayer, Calithera, Acceleron, EUSA, Eisai. T.K. Choueiri: Research Funding: Pfizer, GSK, Novartis, Bristol-Myers Squib, Merck, Exelixis, Roche, AstraZeneca, Tracon, Peloton; Consulting Role: Pfizer, GSK, Novartis, Merck, Bayer, Eisai, Roche, Prometheus Labs Inc, Bristol-Myers Squib, Foundation Medicine Inc. All other authors have declared no conflicts of interest.