https://doi.org/10.1177/1758835919864236 https://doi.org/10.1177/1758835919864236 Therapeutic Advances in Medical Oncology journals.sagepub.com/home/tam 1 Ther Adv Med Oncol 2019, Vol. 11: 1–9 DOI: 10.1177/ 1758835919864236 © The Author(s), 2019. Article reuse guidelines: sagepub.com/journals- permissions Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 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 Giuseppe Gullo, Alex J. Eustace , Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, 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 C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne * and John Crown * Abstract 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/m 2 ). 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. Keywords: bevacizumab, breast cancer, cardiotoxicity biomarker, docetaxel/cyclophosphamide Received: 14 August 2018; revised manuscript accepted: 29 May 2019. *Both authors contributed equally to this article. Correspondence to: John Crown Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland Molecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland john.crown@ccrt.ie Giuseppe Gullo Cancer Trials Ireland (formerly All-Ireland Clinical Oncology Research Group), Dublin Ireland Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland UCD School of Medicine, University College Dublin, Dublin, Ireland Alex J. Eustace Alexandra Canonici Denis M. Collins Norma O’Donovan Molecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland Michael J. Kennedy Department of Medical Oncology, St James Hospital, Dublin, Ireland Liam Grogan Oscar Breathhnach Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland John McCaffrey Department of Medical Oncology, Mater Hospital, Dublin, Ireland Maccon Keane Gregory Leonard Paul Donnellan Department of Medical Oncology, University Hospital Galway, Galway, Ireland Michael J. Martin Department of Medical Oncology, Sligo University Hospital, Sligo, Ireland 864236TAM 0 0 10.1177/1758835919864236Therapeutic Advances in Medical OncologyG Gullo, A Eustace research-article2019 2019 Original Research