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.
Wardley, Andrew M
AffiliationLuca Gianni, Ospedale San Raffaele; Paola Mariani, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan; Mauro Mansutti, University Hospital of Udine, Udine, Italy; Gilles H. Romieu, Centre Régionale de Lutte contre le Cancer, Val d'Aurelle, Montpellier; Xavier Pivot, University Hospital Jean Minjoz, Besançon; Fabrice Andre, Gustave Roussy Institute, Villejuif, France; Michail Lichinitser, N.N. Blokhin Russian Oncology Research Center, Moscow; Oleg Lipatov, Republican Clinical Oncology Dispensary, Ufa; Vladimir Semiglazov, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russian Federation; Sergio V. Serrano, Fundação Pio XII Hospital de Câncer de Barretos, Barretos, Brazil; Arlene Chan, Mount Hospital, Perth, Australia; Stephen Chan, Nottingham University Hospitals National Health Service (NHS) Trust, Nottingham; Andrew Wardley, The Christie NHS Foundation Trust, Manchester, United Kingdom; Richard Greil, Paracelsus Medical University, Salzburg, Austria; and Nicola Moore, Sylvie Prot, and Celine Pallaud, F. Hoffmann-La Roche, Basel, Switzerland.
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AbstractPURPOSEThe 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 METHODSPatients 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.ResultsBaseline 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). CONCLUSIONCombining 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.
CitationAVEREL: 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. 2013: J Clin Oncol
JournalJournal of Clinical Oncology
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