Tony Mok1, Vera Gorbunova, Erzsebet Juhasz, Barna Szima, Olga Burdaeva, Sergey Orlov, Chong-Jen Yu, Venice Archer, Magalie Hilton, Paul Delmar, Celine Pallaud, Martin Reck. 1. *State Key Laboratory of Southern China, Hong Kong Cancer Institute, Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong, China; †Russian Research Oncology Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences, Moscow, Russia; ‡Országos Korányi TBC és Pulmonológiai Intézet, Budapest, Hungary; §Department of Pulmonology, Markusovszky University Hospital, Budapest, Hungary; ‖Arkhangelsk Regional Clinical Oncology Dispensary, Perm, Russia; ¶Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan; #Roche Products Limited, Welwyn Garden City, Hertfordshire, United Kingdom; **F. Hoffmann-La Roche Ltd., Basel, Switzerland; and ††Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.
Abstract
INTRODUCTION: Avastin Biomarkers In lunG And 3D Innovative anaLysis (ABIGAIL), which is a phase II, open-label, randomized study, investigated correlations between biomarkers and best overall response to bevacizumab plus platinum-doublet chemotherapy for patients with advanced/recurrent non-small-cell lung cancer. METHODS: Patients received bevacizumab (7.5 or 15 mg/kg, 3-weekly until disease progression/unacceptable toxicity) plus carboplatin/gemcitabine or carboplatin/paclitaxel (maximum six cycles). Plasma samples (baseline/throughout treatment) were analyzed for vascular endothelial growth factor (VEGF)-A (baseline only), VEGF receptors (VEGFR-1/VEGFR-2), basic fibroblast growth factor, E-selectin, intercellular adhesion molecule-1, and placental growth factor (baseline only). Tumor samples (primary specimen) were analyzed for VEGF-A, VEGFR-1/VEGFR-2, neuropilin (NRP), and CD31. Response was evaluated at baseline and every 6 weeks (Response Evaluation Criteria in Solid Tumors). RESULTS: Patients were randomized to receive chemotherapy plus 7.5 mg/kg (n =154) or 15 mg/kg (n =149) bevacizumab. For the primary analysis, none of the baseline plasma biomarkers correlated with best overall response. Exploratory analyses showed that low VEGF-A levels were associated with longer progression-free survival (7.4 versus 6.1 months; hazard ratio, 1.57; 95% confidence intervals, 1.17 to 2.09; p = 0.002) and overall survival (19.8 versus 11.1 months; hazard ratio, 1.57; 95% confidence interval, 1.15-2.13; p = 0.004) compared with these in high baseline plasma VEGF-A levels. No plasma biomarkers changed significantly over time. No significant correlations were observed between tumor biomarkers and clinical outcomes. No new safety signals were observed. CONCLUSION: Baseline and/or dynamic changes in plasma basic fibroblast growth factor, E-selectin, intercellular adhesion molecule-1, placental growth factor, VEGFR-1 and VEGFR-2, and tumor biomarkers did not correlate statistically with treatment outcomes for bevacizumab plus chemotherapy. Only baseline plasma VEGF-A was significantly correlated with progression-free survival/overall survival.
RCT Entities:
INTRODUCTION:Avastin Biomarkers In lunG And 3D Innovative anaLysis (ABIGAIL), which is a phase II, open-label, randomized study, investigated correlations between biomarkers and best overall response to bevacizumab plus platinum-doublet chemotherapy for patients with advanced/recurrent non-small-cell lung cancer. METHODS:Patients received bevacizumab (7.5 or 15 mg/kg, 3-weekly until disease progression/unacceptable toxicity) plus carboplatin/gemcitabine or carboplatin/paclitaxel (maximum six cycles). Plasma samples (baseline/throughout treatment) were analyzed for vascular endothelial growth factor (VEGF)-A (baseline only), VEGF receptors (VEGFR-1/VEGFR-2), basic fibroblast growth factor, E-selectin, intercellular adhesion molecule-1, and placental growth factor (baseline only). Tumor samples (primary specimen) were analyzed for VEGF-A, VEGFR-1/VEGFR-2, neuropilin (NRP), and CD31. Response was evaluated at baseline and every 6 weeks (Response Evaluation Criteria in Solid Tumors). RESULTS:Patients were randomized to receive chemotherapy plus 7.5 mg/kg (n =154) or 15 mg/kg (n =149) bevacizumab. For the primary analysis, none of the baseline plasma biomarkers correlated with best overall response. Exploratory analyses showed that low VEGF-A levels were associated with longer progression-free survival (7.4 versus 6.1 months; hazard ratio, 1.57; 95% confidence intervals, 1.17 to 2.09; p = 0.002) and overall survival (19.8 versus 11.1 months; hazard ratio, 1.57; 95% confidence interval, 1.15-2.13; p = 0.004) compared with these in high baseline plasma VEGF-A levels. No plasma biomarkers changed significantly over time. No significant correlations were observed between tumor biomarkers and clinical outcomes. No new safety signals were observed. CONCLUSION: Baseline and/or dynamic changes in plasma basic fibroblast growth factor, E-selectin, intercellular adhesion molecule-1, placental growth factor, VEGFR-1 and VEGFR-2, and tumor biomarkers did not correlate statistically with treatment outcomes for bevacizumab plus chemotherapy. Only baseline plasma VEGF-A was significantly correlated with progression-free survival/overall survival.
Authors: J De Castro; J L González-Larriba; S Vázquez; B Massutí; J M Sanchez-Torres; M Dómine; P Garrido; A Calles; A Artal; R Collado; R García; M Sereno; M Majem; J A Macías; O Juan; J Gómez-Codina; B Hernández; M Lázaro; A L Ortega; M Cobo; J M Trigo; E Carcereny; C Rolfo; S Macia; J Muñoz; P Diz; M Méndez; F Rosillo; L Paz-Ares; J V Cardona; D Isla Journal: Clin Transl Oncol Date: 2016-07-01 Impact factor: 3.405