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)

• Published in: Journal of thoracic oncology Vol. 9; no. 6; pp. 848 - 855
• Main Authors: Mok, Tony, Gorbunova, Vera, Juhasz, Erzsebet, Szima, Barna, Burdaeva, Olga, Orlov, Sergey, Yu, Chong-Jen, Archer, Venice, Hilton, Magalie, Delmar, Paul, Pallaud, Celine, Reck, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2014; Copyright by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer
• Subjects: Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biomarker; Biomarkers, Tumor - analysis; Biomarkers, Tumor - blood; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease-Free Survival; E-Selectin - blood; Female; Fibroblast Growth Factor 2 - blood; Humans; Intercellular Adhesion Molecule-1 - blood; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Male; Neuropilins - analysis; Non–small-cell lung cancer; Paclitaxel - administration & dosage; Placenta Growth Factor; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Pregnancy Proteins - blood; Prospective Studies; Survival Rate; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor Receptor-1 - analysis; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-2 - analysis; Vascular Endothelial Growth Factor Receptor-2 - blood; Non–small-cell lung cancer; Biomarker; Vascular endothelial growth factor; Bevacizumab
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1097/JTO.0000000000000160

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. 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). 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. 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.