1236PD - Tumour Biomarker and Plasma Time Course Data from Abigail, A Phase II Study of 1st-Line Bevacizumab + Chemotherapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer (NS-NSCLC)

Abstract

ABSTRACT Background BO21015 (NCT00700180) is a phase II, randomized, multicentre study exploring correlation between biomarkers (BMs) and best overall response (BOR) to bevacizumab with carboplatin/gemcitabine (CG) or carboplatin/paclitaxel (CP) in chemonaive patients with advanced/recurrent NSCLC. Efficacy, safety and correlation of 7 baseline (BL) plasma BM (bFGF, E-selectin, ICAM, PLGF, VEGFA, VEGFR-1 and VEGFR-2) with BOR and progression-free survival (PFS) have been reported.1 This abstract presents BM analysis for tumour tissue, plasma time course and clinical outcome. Methods 303 eligible patients were randomized 1:1 to receive bevacizumab 7.5 mg/kg or 15 mg/kg until disease progression (PD) or unacceptable toxicity (with 6 cycles of CG or CP, at investigators' discretion). Consented patients provided blood1 and tumour samples for BM analysis. Pre-specified exploratory analyses examined correlation between BL plasma BM and overall survival (OS) and changes in plasma BM levels from BL to PD, cycles 2, 4 and 6. Plasma BM levels were measured by ELISA. IHC analyses of 5 tumour BMs (VEGFR-1, MVD, VEGFA, VEGFR-2 and NRP1) were assessed for correlation with BOR, PFS and OS, and with BL plasma BM levels. Results \Further exploratory analyses adjusting for BL prognostic factors and accounting for multiple testing showed a correlation of high BL VEGFA levels (3median) with shorter OS (n = 280; 19.8 vs 11.1 mos; p = 0.0042). No other BL plasma BMs correlated with OS. No significant changes in plasma BM levels were seen between baseline and PD, and/or cycles 2, 4 or 6 for any of the BMs. The only correlation between tumour and plasma markers was for tumour VEGFR1 expression and VEGFA plasma BL (p = 0.025, 0.26). No significant correlation was seen between tumour BM level and BOR, PFS or OS. Conclusions Exploratory analysis showed high plasma BL VEGFA significantly correlated with shorter OS, consistent with previously reported data on PFS. No other BL plasma BMs correlated with OS. BL plasma VEGFA levels correlated with tumour VEGFR1 expression. None of the investigated tumour BMs significantly correlated with clinical outcome. 1 Mok et al. ESMO 2011 Disclosure M. Reck: Attended advisory boards for Roche, Lilly, BMS, AstraZeneca and Daiichi Sankyo. Received honoraria for lectures from Roche, Lilly, Daiichi Sankyo and AstraZeneca. V.A. Gorbunova: Attended advisory boards with Novartis and Pfizer. Honoraria for lectures from Roche and Bayer. B. Szima: Received funding for research. C. Yu: Attended advisory boards for Roche, AstraZeneca, Pfizer and Takeda. C. Pallaud: Owns stock in Roche. Currently employed by Roche. S.J. Scherer: Currrently employed by Roche/Genentech. V. Archer: Currently employed by Roche. T.S.K. Mok: Advisory boards: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene, AVEO, Pfizer, Taiho, BI, GSK Biologicals. On the IASLC board of directors. Received research funding from AstraZeneca. Employed by The Chinese Uinversity of Hong Kong. All other authors have declared no conflicts of interest.