title: A correlative biomarker analysis of the combination of bevacizumab and carboplatin-based chemotherapy for advanced nonsquamous non-small-cell lung cancer: results of the phase II randomized ABIGAIL study (BO21015).
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: *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.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Juhasz
authors.forename: Barna
authors.initials: B
authors.lastname: Szima
authors.forename: Olga
authors.initials: O
authors.lastname: Burdaeva
authors.forename: Sergey
authors.initials: S
authors.lastname: Orlov
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Venice
authors.initials: V
authors.lastname: Archer
authors.forename: Magalie
authors.initials: M
authors.lastname: Hilton
authors.forename: Paul
authors.initials: P
authors.lastname: Delmar
authors.forename: Celine
authors.initials: C
authors.lastname: Pallaud
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D019040:E-Selectin / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D039921:Neuropilins / Q000032:analysis; D017239:Paclitaxel / Q000008:administration & dosage; D000072483:Placenta Growth Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011257:Pregnancy Proteins / Q000097:blood; D011446:Prospective Studies; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000097:blood; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D019040:E-Selectin; D039921:Neuropilins; C000608036:PGF protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1; D000072483:Placenta Growth Factor; D000068258:Bevacizumab; D016190:Carboplatin; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D017239:Paclitaxel; D000093542:Gemcitabine