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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2013

01-06-2013 | Clinical trial

A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer

Authors: N. U. Lin, D. S. Seah, R. Gelman, S. Desantis, E. L. Mayer, S. Isakoff, P. DiPiro, I. E. Krop, S. E. Come, D. Weckstein, E. P. Winer, H. J. Burstein

Published in: Breast Cancer Research and Treatment | Issue 2/2013

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Abstract

We aimed to evaluate the efficacy and feasibility of combining trastuzumab/vinorelbine with bevacizumab in patients with first-or second-line HER2-positive, metastatic breast cancer (MBC). Eligible patients had HER2-positive measureable MBC, with no more than one prior line of chemotherapy, and were treated with trastuzumab (4 mg/kg × 2 mg/kg weekly thereafter), vinorelbine (25 mg/m2 weekly), and bevacizumab (10 mg/kg every 2 weeks). Co-primary endpoints were (a) the proportion of patients alive and progression-free at 1 year and (b) safety profile/feasibility. Feasibility was defined as a rate of grade 3/4 non-hematologic toxicity attributable to protocol-based therapy <20 %. Twenty-nine patients were enrolled (n = 22 first-line, n = 7 second-line). Median age was 48 years (range 37–68). The median number of cycles received was 8 (1–23) and median duration on treatment was 7.4 months (range 1–22). The study was closed early due to higher-than-expected rates of grade 3/4 non-hematologic toxicities, with 50 events in 20 patients. A total of six patients (21 %) were taken off study for treatment-related toxicity. Most common treatment-related toxicities included fatigue (n = 7), febrile neutropenia (n = 4), and headache (n = 3). At 1 year, 8/22 first-line (36 %) and 2/7 second-line (29 %) patients were alive and progression-free. Median PFS was 9.9 months and 7.8 months in the first- and second-line cohorts, respectively. Objective responses were observed in 16/22 (73 %) and 5/7 (71 %) patients in the first- and second-line settings. Although the combination of vinorelbine, trastuzumab, and bevacizumab showed notable activity in HER2-positive MBC, the proportion of first-line patients alive and progression-free at 1 year was deemed unlikely to reach the pre-defined threshold for declaring success. Additionally, unacceptable toxicity was observed, at rates greater than previously reported with vinorelbine/trastuzumab or vinorelbine/bevacizumab doublet combinations.
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Literature
1.
Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182PubMedCrossRef
2.
Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRef
3.
Burstein HJ, Kuter I, Campos SM et al (2001) Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol 19:2722–2730PubMed
4.
Lin NU, Winer EP (2011) Chemotherapy agents in human epidermal growth factor receptor 2-positive breast cancer: time to step out of the limelight. J Clin Oncol 29:251–253PubMedCrossRef
5.
Burstein HJ, Harris LN, Marcom PK et al (2003) Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. J Clin Oncol 21:2889–2895PubMedCrossRef
6.
Burstein HJ, Keshaviah A, Baron AD et al (2007) Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer 110:965–972PubMedCrossRef
7.
Andersson M, Lidbrink E, Bjerre K et al (2011) Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol 29:264–271PubMedCrossRef
8.
Konecny GE, Meng YG, Untch M et al (2004) Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 10:1706–1716PubMedCrossRef
9.
Pegram M, Chan D, Dichmann RA et al (2006) Phase II combined biological therapy targeting the HER-2 proto-oncogene and the vascular endothelial growth factor using trastuzumab (T) and avastin (B) as first-line treatment of HER2-amplified breast cancer. Breast Cancer Res Treat 100:abstr 301
10.
Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676PubMedCrossRef
11.
Burstein HJ, Chen YH, Parker LM et al (2008) VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res 14:7871–7877PubMedCrossRef
12.
Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRef
13.
Brufsky AM, Hurvitz S, Perez E et al (2011) RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 29:4286–4293PubMedCrossRef
14.
Robert NJ, Dieras V, Glaspy J et al (2011) RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 29:1252–1260PubMedCrossRef
15.
Miles DW, Chan A, Dirix LY et al (2010) Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 28:3239–3247PubMedCrossRef
16.
Arteaga CL, Mayer IA, O’Neill AM et al (2012) A randomized phase III double-blinded placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-overexpressing metastatic breast cancer (HER2 + MBC): A trial of the Eastern Cooperative Oncology Group (E1105). J Clin Oncol (suppl; abstr 605)
17.
Gianni L, Romieu G, Lichinitser M et al (2011) AVEREL, a randomized phase III trial to evaluate bevacizumab in combination with trastuzumab + docetaxel as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. In: San Antonio Breast Cancer Symposium, TX, December 6–11, 2011
Metadata
Title
A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer
Authors
N. U. Lin
D. S. Seah
R. Gelman
S. Desantis
E. L. Mayer
S. Isakoff
P. DiPiro
I. E. Krop
S. E. Come
D. Weckstein
E. P. Winer
H. J. Burstein
Publication date
01-06-2013
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-013-2551-9

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