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Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial.

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posted on 10.11.2020, 18:01 by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J Kennedy, Liam Grogan, Oscar Breathnach, John McCaffrey, Maccon Keane, Michael J Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice O'Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette Byrne, John Crown

Background: Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients.

Methods: Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m2). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF).

Results: A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1-72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12-54) months in TN patients versus 38 (22-71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity.

Conclusions: We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further.

Trial registration: ClinicalTrials.gov Identifier: NCT00911716.

Funding

AngioTox (www. angiotox.com), a European Commission FP7 Industry Academia Pathways and Partnerships Marie Curie Award (grant agreement 251528).

Irish Cancer Society Collaborative Cancer Research Centre under BREAST-PREDICT (www.breastpredict.com; grant number CCRC13GAL).

Sanofi Aventis.

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The original article is available at https://journals.sagepub.com

Published Citation

Gullo G, Eustace AJ, Canonici A, M Collins DM, Kennedy MJ, Grogan L, Breathhnach O, McCaffrey J, Keane M, Martin MJ, Gupta R, Leonard G, O'Connor M, Calvert PM, Donnellan P, Walshe J, McDermott E, Scott K, Hernando A, Parker I, Murray DW, O'Farrell AC, Maratha A, Dicker P, Rafferty M, Murphy V, O'Donovan N, Gallagher WM, Ky B, Tryfonopoulos D, Moulton B, Byrne AT, Crown J. Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08-10 trial. Therapeutic Advances in Medical Oncology. 2019;11:1–9

Publication Date

24 Jul 2019

PubMed ID

31384312

Department/Unit

  • Public Health and Epidemiology
  • Beaumont Hospital
  • Physiology and Medical Physics

Research Area

  • Population Health and Health Services
  • Cancer

Publisher

SAGE Publications

Version

  • Published Version (Version of Record)

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