842P - Biomarkers of Everolimus Efficacy in Patients with Metastatic Renal Cell Carcinoma (MRCC): Analysis of the Phase III Record-1 Trial

Abstract

ABSTRACT Background In RECORD-1, everolimus significantly increased median PFS (primary end point) over placebo in VEGFr-TKI-refractory patients with mRCC. We investigated angiogenesis pathway molecules, sVEGFR-2, VEGF-A, and bFGF, in plasma as potential biomarkers of everolimus efficacy in RECORD-1. Material and methods Patients received everolimus 10 mg daily (n = 277) or placebo (n = 139), both with BSC; placebo patients could cross over to everolimus at disease progression. Pre-dose blood samples were collected on day 1 of the first four 28-day treatment cycles; plasma levels of sVEGFR-2, VEGF-A, and bFGF were assessed using ELISA. A mixed effects model was used to assess treatment effect over time on each biomarker. Hazard ratios (HR) for prognostic effects were obtained using log baseline biomarker values as continuous variables in a stratified Cox proportional hazards model. Results Plasma values for sVEGFR-2, VEGF-A, and bFGF were available for 45/45/39% of everolimus patients and 50/50/45% of placebo patients. Baseline characteristics of patients with biomarker data were similar to the overall population. Mean log baseline values for sVEGFR-2, VEGF-A, and bFGF were similar for both arms; 9.1/5.1/1.6 for everolimus and 9.1/5.2/1.8 for placebo, respectively. Median PFS was significantly improved with everolimus vs placebo, regardless of baseline levels of any of the biomarkers analyzed (P Conclusions Everolimus provided significant clinical benefit over placebo, regardless of baseline biomarker levels. However, lower VEGF-A level was seen as a potential prognostic factor for longer PFS. Plasma levels of bFGF and sVEGFR-2 were significantly down-regulated from baseline by everolimus treatment. Disclosure S. Oudard: Stephane Oudard received honoraria from Bayer, Novartis, Pfizer, Roche, and Sanofi-Aventis. B. Escudier: Bernard Escudier has received honorarium from Novartis, Pfizer, GSK, Aveo, and Bayer. J. Thompson: John Thompson received clinical study support from Novartis. V. Grunwald: Viktor Grunwald served as consultant to Roche, Bayer, Novartis, Pfizer, GlaxoSmithKline, and Aveo/Astellas, received honoraria from GlaxoSmithKline, Novartis, and Pfizer, and received research funding from Pfizer and GlaxoSmithKline. S. Bracarda: Sergio Bracarda has served as advisor for Pfizer, Bayer-Schering, GlaxoSmithKline, Novartis, Aveo/Astellas, Boheringer-Ingelheim, Johnson & Johnson, and Sanofi-Aventis and has received speaker fees from Pfizer, Novartis, and Sanofi-Aventis. A. Panneerselvam: Ashok Panneerselvam is an employee of Novartis Pharmaceuticals Corporation. S. Gogov: Sven Gogov is an employee of Novartis Pharma AG. D. Chen: David Chen is an employee of Novartis Pharmaceuticals Corporation. R.J. Motzer: Robert Motzer has received research funding from Novartis. All other authors have declared no conflicts of interest.