AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer

PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurren...

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Veröffentlicht in:Journal of clinical oncology Jg. 31; H. 14; S. 1719
Hauptverfasser: Gianni, Luca, Romieu, Gilles H, Lichinitser, Michail, Serrano, Sergio V, Mansutti, Mauro, Pivot, Xavier, Mariani, Paola, Andre, Fabrice, Chan, Arlene, Lipatov, Oleg, Chan, Stephen, Wardley, Andrew, Greil, Richard, Moore, Nicola, Prot, Sylvie, Pallaud, Celine, Semiglazov, Vladimir
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 10.05.2013
Schlagworte:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bevacizumab
Biomarkers, Tumor - analysis
Biomarkers, Tumor - blood
Breast Neoplasms - chemistry
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Carcinoma, Ductal, Breast - drug therapy
Carcinoma, Lobular - drug therapy
Disease-Free Survival
Drug Administration Schedule
Female
Humans
Hypertension - chemically induced
Hypertension - epidemiology
Inflammatory Breast Neoplasms - drug therapy
Middle Aged
Neoplasm Recurrence, Local - chemistry
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - pathology
Neoplasm Staging
Neutropenia - chemically induced
Neutropenia - epidemiology
Quality of Life
Receptor, ErbB-2 - analysis
Surveys and Questionnaires
Taxoids - administration & dosage
Trastuzumab
Treatment Outcome
Vascular Endothelial Growth Factor A - blood
ISSN:1527-7755, 1527-7755
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Zusammenfassung:PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurrent/metastatic breast cancer (LR/MBC). PATIENTS AND METHODS Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m(2) plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). Additional end points included overall survival, response rate (RR), safety, quality of life, and translational research. Results Baseline characteristics of the 424 patients were balanced between treatment arms. Most patients had visceral metastases, 43% had a disease-free interval less than 12 months, and 85% had measurable disease. Median follow-up was 26 months. The hazard ratio for investigator-assessed PFS was 0.82 (95% CI, 0.65 to 1.02; P = .0775; median PFS, 13.7 v 16.5 months in the non-bevacizumab and bevacizumab arms, respectively; PFS events in 72%). The Independent Review Committee-assessed PFS hazard ratio was 0.72 (95% CI, 0.54 to 0.94; P = .0162; median PFS, 13.9 v 16.8 months, respectively; PFS events in 53%). The RR was 70% versus 74%, respectively (P = .3492). Grade ≥ 3 febrile neutropenia and hypertension were more common with bevacizumab-containing therapy. High baseline plasma vascular endothelial growth factor A (VEGF-A) concentrations were associated with greater bevacizumab benefit (not statistically significant). CONCLUSION Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigator-assessed PFS. The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.
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ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.2012.44.7912