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).
Bevacizumab
Breast cancer
Chemotherapy
Trastuzumab
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
05 Jul 2024
05 Jul 2024
Historique:
received:
19
04
2024
accepted:
23
06
2024
medline:
5
7
2024
pubmed:
5
7
2024
entrez:
5
7
2024
Statut:
aheadofprint
Résumé
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. 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. 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. NCT00520975.
Sections du résumé
BACKGROUND
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
RESULTS
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
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
BACKGROUND
NCT00520975.
Identifiants
pubmed: 38967884
doi: 10.1007/s10549-024-07417-4
pii: 10.1007/s10549-024-07417-4
doi:
Banques de données
ClinicalTrials.gov
['NCT00520975']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : UG1CA233270
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233270
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233302
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233320
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA189828
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233320
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA190140
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA189805
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA189830
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233320
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233270
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA189954
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : U10CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233196
Pays : United States
Organisme : NCI NIH HHS
ID : UG1CA233270
Pays : United States
Organisme : CCR NIH HHS
ID : UG1CA233234
Pays : United States
Informations de copyright
© 2024. The Author(s).
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