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)
Year: 2024
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Authors: Jessica Mezzanotte-Sharpe, Anne ONeill, Ingrid A. Mayer, Carlos L. Arteaga, Ximing J. Yang, Lynne I. Wagner, David Cella, Neal J. Meropol, R. Katherine Alpaugh, Thomas J. Saphner, Robert E. Swaney, Karen L. Hoelzer, William J. Gradishar, Vandana G. Abramson, P. Kothai Sundaram, Shamim Z. Jilani, Edith A. Perez, Nancy U. Lin, Mohammad Jahanzeb, Antonio C. Wolff, George W. Sledge, Sonya A. Reid
Institutions: Vanderbilt University Medical Center, Dana-Farber Cancer Institute, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Northwestern University, Wake Forest University Health Sciences, Wake Forest University, Case Western Reserve University, Fox Chase Cancer Center, Aurora Health Care, Denver Health Medical Center, Memorial Medical Center, Good Samaritan Hospital, Mayo Clinic in Florida, University of Miami, Johns Hopkins University, Stanford Cancer Institute
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,990
Awards: G1881030900, ECOG-ACRIN Network Group Operations Center, G1938688226, G1946161885, G1980229645, G2117393317, G2398472636, G2424276686, Dayton Clinical Oncology Program, G2819266960, G3231584006, Western States Cancer Research NCORP, G3475623468, ECOG-ACRIN NCORP Research Base, G4892314745, G5417201949, Aurora NCORP Community Site, NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer Care, G580335595, NCI, National Clinical Trials Network Lead Academic Participating Site (LAPS) UG1, G6536185887, G6705915398, G6952446453, Johns Hopkins University NCTN Lead Academic Site Program, G8220656038, Vanderbilt Network Lead Academic Participating Site for the NCTN, Alliance for Clinical Trials in Oncology Operations Center, G9000012443, G9000086563, G9000097678, G9000327439
OpenAlex ID: W4400370176