A randomized phase III double-blind placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-positive metastatic breast cancer: A trial of the ECOG-ACRIN Cancer Research Group (E1105)

Jessica Mezzanotte-Sharpe, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 PRB, Nashville, TN, 37232-6307, USA.
Anne ONeill, Dana-Farber Cancer Institute, Boston, MA, USA.
Ingrid A. Mayer, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 PRB, Nashville, TN, 37232-6307, USA.
Carlos L. Arteaga, UT Southwestern/Simmons Cancer Center, Dallas, TX, USA.
Ximing J. Yang, Northwestern University, Chicago, IL, USA.
Lynne I. Wagner, Wake Forest University Health Sciences, Winston Salem, NC, USA.
David Cella, Northwestern University, Chicago, IL, USA.
Neal J. Meropol, Case Western Reserve University, Cleveland, OH, USA.
R Katherine Alpaugh, Fox Chase Cancer Center, Philadelphia, PA, USA.
Thomas J. Saphner, Advocate Health - MidwestFollow
Robert E. Swaney, Denver Health Medical Center, Denver, CO, USA.
Karen L. Hoelzer, Memorial Medical Center, Springfield, IL, USA.
William J. Gradishar, Northwestern University, Chicago, IL, USA.
Vandana G. Abramson, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 PRB, Nashville, TN, 37232-6307, USA.
P Kothai Sundaram, Columbus NCORP, Columbus, OH, USA.
Shamim Z. Jilani, Good Samaritan Hospital, Dayton, OH, USA.
Edith A. Perez, Mayo Clinic, Jacksonville, FL, USA.
Nancy U. Lin, Dana-Farber Cancer Institute, Boston, MA, USA.
Mohammad Jahanzeb, University of Miami, Deerfield Beach, FL, USA.
Antonio C. Wolff, Johns Hopkins University, Baltimore, MD, USA.
George W. Sledge, Stanford Cancer Institute, Stanford, CA, USA.
Sonya A. Reid, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 PRB, Nashville, TN, 37232-6307, USA. sonya.reid@vumc.org.

Affiliations

Aurora Cancer Care, Two Rivers

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.

Document Type

Article

PubMed ID

38967884

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