1236PD - Tumour biomarker and plasma time course data from ABIGAIL, a phase II study of 1st-line bevacizumab + chemotherapy in advanced non-squamous non-smal...

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Martin Reck
Authors M. Reck1, V.A. Gorbunova2, E. Juhász3, B. Szima4, S. Orlov5, C. Yu6, C. Pallaud7, S.J. Scherer8, V. Archer9, T.S.K. Mok10
  • 1Thoracic Oncology, Hospital Grosshansdorf, 22926 - Grosshansdorf/DE
  • 2Department Of Chemotherapy, Russian Research Oncology Center n.a. N. N. Blokhin Russian Cancer Research Center, Moscow/RU
  • 3Pulmonology Department Xiv, Országos Korányi TBC és Pulmonologiai Intézet, Budapest/HU
  • 4Department Of Oncoradiology, Markusovszky Hospital, Szombathely/HU
  • 5Laboratory Of Thoracic Oncology, St Petersburg State Medical University, St Petersburg/RU
  • 6Department Of Internal Medicine, National Taiwan University Hospital, Taipei/TW
  • 7Pharma Development Oncology Department, F. Hoffmann-La Roche Ltd., Basel/CH
  • 8Pharma Development Department, Genentech, San Francisco/US
  • 9Clinical Development (oncology), Roche Products Ltd., Welwyn Garden City/UK
  • 10Department Of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong/HK

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 chemonaïve 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.