Original Articles
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)

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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.

Key words

Non–small-cell lung cancer
Biomarker
Bevacizumab
Vascular endothelial growth factor

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Disclosure: Tony Mok is a consultant for, and has received honorarium from, AstraZeneca, Eli Lilly, Merck Serono, Eisai, BMS, Biogene, AVEO, Pfizer, Taiho, Boehringer Ingelheim, GSK Biologicals, and has received research funding from AstraZeneca. Celine Pallaud, Magalie Hilton, Paul Delmar and Venice Archer are employees of F. Hoffmann-La Roche Ltd. Martin Reck is a consultant for, and has received honorarium from, BMS, Daiichi Sankyo and AstraZeneca. Chong-Jen Yu, Barna Szima, Sergey Orlov, Erzsebet Juhasz, Vera Gorbunova and Olga Burdaeva have no conflicts of interest to declare.