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A Phase II study of bevacizumab in combination with trastuzumab and docetaxel in HER2 positive metastatic breast cancer

  • PHASE II STUDIES
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Summary

Background Preclinical and early clinical data support the use of Vascular Epithelial Growth Factor (VEGF)-targeted therapy with trastuzumab in Human Epidermal Receptor 2 (HER2) positive breast cancer. Adding bevacizumab to a taxane (docetaxel or paclitaxel) improves progression free survival (PFS) of metastatic breast cancer (MBC) patients. Objectives We evaluated the efficacy and feasibility of combining bevacizumab with trastuzumab and docetaxel in patients with HER2- positive MBC who received 0–1 prior chemotherapy regimens for metastatic disease. The primary end point was PFS. Materials and Methods Eligible patients received bevacizumab (15 mg/kg), trastuzumab (8 mg/kg loading dose followed by 6 mg/kg), and docetaxel (100 mg/m2 initially, later amended to 75 mg/m2) every three weeks for six cycles and then were allowed to receive bevacizumab and trastuzumab alone. Results Thirteen (50 %) of 26 patients enrolled completed all 6 cycles of bevacizumab, trastuzumab and docetaxel and went on to receive bevacizumab and trastuzumab alone (median: 11 cycles). The most common grade 3 or 4 toxicities include: neutropenia (8 %), septic death (4 %), infection not associated with neutropenia (15 %), fatigue (27 %), mylagia and/or arthraligia (20 %), and hand-foot syndrome (8 %). One patient (4 %) and six patients (23 %) developed grade 3 and grade 2 hypertension, respectively. Two (8 %) patients had transient grade 2 drop in Left Ventricular Ejection Fraction (LVEF) with full recovery later. The median progression free survival (PFS) was 14.3 months (95 % CI: 9.3–35 months), the objective response rate (ORR), defined as the best response of complete response (CR) or partial response (PR) was (12/26) 46 %. The clinical benefit rate (CBR), defined as the best response of CR or PR or stable disease (SD) for at least 24 weeks, was (18/26) 69 % (95 % CI: 48–86 %). Conclusion The combination of bevacizumab, trastuzumab and docetaxel is well tolerated and is clinically active in patients with HER2-positive MBC, with response rate and PFS comparable to previous reports utilizing higher dose of docetaxel (100 mg/m2). Recent randomized trials did not demonstrate additional overall survival (OS) benefit of adding bevacizumab to trastuzumab and docetaxel despite an improvement in PFS. Identification of predictive biomarkers and careful patient selection should be incorporated in further investigation of anti-VEGF in breast cancer.

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Conflict of interest disclosure

Dr. Bhuvaneswari Ramaswamy had disclosed that she had served on the advisory board for Genentech.

Ethical approval

All patients signed an informed consent form prior to enrollment in the study. Local ethical approval was received and the study was conducted in accordance with the Ohio State University and University of Pittsburgh Institutional Review Boards.

Funding

This work was supported by Genentech.

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Authors and Affiliations

  1. Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, The Ohio State University’s Wexner Medical Center, Starling-Loving Hall, 320 W 10th Ave, Columbus, OH, 43210, USA

    Meng Zhao, Rachel Layman, Maryam B. Lustberg, Ewa Mrozek, Erin R. Macrae, Robert Wesolowski, Sarah Carothers, Charles L. Shapiro, Bhuvaneswari Ramaswamy & Bhuvaneswari Ramaswamy

  2. Center for Biostatistics, The Ohio State University, 2012 Kenny Road, Columbus, OH, 43221, USA

    Xueliang Pan

  3. University of Pittsburgh Medical Center, 300 Halket Str. Suite 4628, Pittsburgh, PA, 15123, USA

    Shannon Puhalla

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Zhao, M., Pan, X., Layman, R. et al. A Phase II study of bevacizumab in combination with trastuzumab and docetaxel in HER2 positive metastatic breast cancer. Invest New Drugs 32, 1285–1294 (2014). https://doi.org/10.1007/s10637-014-0122-5

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