Author:
Mezzanotte-Sharpe Jessica,ONeill Anne,Mayer Ingrid A.,Arteaga Carlos L.,Yang Ximing J.,Wagner Lynne I.,Cella David,Meropol Neal J.,Alpaugh R. Katherine,Saphner Thomas J.,Swaney Robert E.,Hoelzer Karen L.,Gradishar William J.,Abramson Vandana G.,Sundaram P. Kothai,Jilani Shamim Z.,Perez Edith A.,Lin Nancy U.,Jahanzeb Mohammad,Wolff Antonio C.,Sledge George W.,Reid Sonya A.
Abstract
Abstract
Background
In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the pre-clinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC.
Findings
96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43–1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61–1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab.
Conclusions
In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.
Clinical Trial Information: NCT00520975
Funder
National Cancer Institute
Center for Cancer Research
Publisher
Springer Science and Business Media LLC
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