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.
Authors
Gianni, LRomieu, G
Lichinitser, M
Serrano, S
Mansutti, M
Pivot, X
Mariani, P
Andre, F
Chan, A
Lipatov, O
Chan, S
Wardley, Andrew M
Greil, R
Moore, N
Prot, S
Pallaud, C
Semiglazov, V
Affiliation
Luca 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.Issue Date
2013-04-08
Metadata
Show full item recordAbstract
PURPOSEThe 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.Citation
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. 2013: J Clin OncolJournal
Journal of Clinical OncologyDOI
10.1200/JCO.2012.44.7912PubMed ID
23569311Type
ArticleLanguage
enISSN
1527-7755ae974a485f413a2113503eed53cd6c53
10.1200/JCO.2012.44.7912
Scopus Count
Collections
Related articles
- Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer.
- Authors: Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G
- Issue date: 2010 Jul 10
- RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer.
- Authors: Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J
- Issue date: 2011 Apr 1
- Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study.
- Authors: Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J
- Issue date: 2012 Jul 20
- RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer.
- Authors: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS
- Issue date: 2011 Nov 10
- Trastuzumab retreatment after relapse on adjuvant trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer: final results of the Retreatment after HErceptin Adjuvant trial.
- Authors: Láng I, Bell R, Feng FY, Lopez RI, Jassem J, Semiglazov V, Al-Sakaff N, Heinzmann D, Chang J
- Issue date: 2014 Feb