The first presentation of the BEATRICE trial, evaluating adjuvant Avastin with a physician’s choice taxane- and/or anthracycline-based regimen in patients with triple-negative disease, was at the annual San Antonio Breast Cancer Symposium (SABCS). Given the diminished recent role of Avastin in the metastatic setting and the well-publicized failure of the adjuvant trial in colorectal cancer, these negative results were not too surprising.
Interestingly, Dr. Norman Wolmark is still frustrated that the signal of an impressive reduction in recurrence observed when Avastin was on board in the NSABP-C-08 colon cancer trial has not been further pursued. BEATRICE, like C-08, used one year of Avastin, and Wolmark continues to believe that more benefit would be seen with a greater duration of treatment, although this is not likely to be studied.
Primary Results of BEATRICE, a Randomized Phase III Trial Evaluating Adjuvant Bevacizumab-Containing Therapy in Triple-Negative Breast Cancer
Cameron D, Brown J, Dent R, Jackisch C, Mackey J, Pivot X, Steger G, Suter T, Toi M, Parmar M, Bubuteishvili-Pacaud L, Henschel V, Laeufle R, Bell R. University of Edinburgh and Cancer Services, NHS Lothian, Edinburgh, United Kingdom; University of Leeds, United Kingdom; Sunnybrook Health Sciences Center and University of Toronto, Toronto, ON, Canada; Klinikum Offenbach, Offenbach, Germany; Cross Center Institute, Edmonton, Canada; University Hospital Jean Minjoz, Besançon, France; Medical University of Vienna, Austria; Bern University Hospital, Inselspital, Switzerland; Kyoto University, Kyoto, Japan; MRC Clinical Trials Unit, London, United Kingdom; F. Hoffmann-La Roche Ltd, Basel, Switzerland; F Hoffmann-La Roche Ltd, Basel, Switzerland; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Andrew Love Cancer Centre, Geelong, Australia; National Cancer Center, Singapore, Singapore
Background:
Bevacizumab (BEV), an anti-VEGF antibody, significantly enhanced progression-free survival in metastatic breast cancer (BC) (E2100, AVADO, RIBBON-1, RIBBON-2) and pathologic complete response rates in the neoadjuvant setting (GeparQuinto, NSABP B-40) when combined with chemotherapy (CT). The dependence of micro-metastases on angiogenesis [Holmgren 1995] suggests that patients might benefit from anti-angiogenic strategies applied in the adjuvant setting. The BEATRICE trial was designed to test this hypothesis in patients with triple-negative BC, who have a poor prognosis and lack targeted options for treatment.
Methods:
In this open-label randomized multinational phase III trial, patients with centrally confirmed triple-negative operable primary invasive BC (pT1a-pT3) were randomized 1:1 after definitive surgery to receive ≥4 cycles of either CT alone or the same CT + 1 year of BEV 5 mg/kg/wk equivalent. CT was anthracycline [anth] and/or taxane-based. Patients were stratified by nodal status (0 vs 1-3 vs ≥4 involved nodes), CT backbone (anth vs anth + taxane vs taxane), hormone receptor status (negative vs low), and surgery (breast-conserving vs mastectomy). The primary objective is to compare invasive disease-free survival (IDFS) [Hudis 2007] with adjuvant CT ± 1 year of BEV. Secondary outcome measures are overall survival (OS), breast cancer-free interval, disease-free survival (DFS), distant DFS, and safety (NCI CTCAE v3.0). The sample size was calculated to provide 80% power for a HR=0.75 at α=0.05 assuming 5-year IDFS of 72.0% with CT vs 78.2% with CT + BEV with 388 events. BEATRICE also includes evaluation of potential predictive and prognostic biomarkers.
Results:
Between Dec 2007 and Mar 2010, 2591 patients were randomized. At data cut-off (Feb 29, 2012), median follow-up was 32 months.
http://www.abstracts2view.com/sabcs1...u=SABCS12L_754
http://www.researchtopractice.com/si...wnloadable.pdf