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.
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.
Analyses of PFS and OS based on baseline biomarker levels showed improvement with C vs E (hazard ratio
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
Legal entity responsible for the study
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.