> Table 49: Trastuzumab (Herceptin) and overall response rate in metastatic breast cancer
This summary table contains detailed information about research studies. While viewing summary tables offers an informative glimpse at the science behind many breast cancer guidelines and recommendations, they should be viewed with some caution. There are a number of concepts you must understand to be able to successfully read and interpret research tables. To get some background information about understanding research tables, please see How to Read a Research Table.
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Introduction: The drug trastuzumab (Herceptin) targets the HER2/neu receptor protein on breast cancer cells. A tumor that is HER2/neu-positive has too much HER2/neu receptor protein (the HER2/neu receptor protein is over-expressed). Studies show that trastuzumab can shrink tumors and improve survival in people whose metastatic breast cancer is HER2/neu-positive. About 20 to 30 percent of people with breast cancer have HER2/neu-positive tumors.
Phase II clinical trials in women with HER2/neu-positive metastatic breast cancer (listed below) have shown that trastuzumab is effective when used alone. They also suggest that its benefit is increased when combined with chemotherapy. One study found that even women whose metastatic cancer had started to progress while on chemotherapy, had close to a 25 percent response rate when trastuzumab was added to the chemotherapy. This means that nearly a quarter of these women had cancer that either shrank or could not be detected after treatment.
Trastuzumab has also been shown to be effective as a first treatment for HER2/neu-positive metastatic breast cancer. Results from phase III clinical trials (listed below) show that combining trastuzumab with chemotherapy improves the response rate compared to using chemotherapy alone.
Trastuzumab tends to cause fewer side effects than standard chemotherapy because it only targets cancer cells with the HER2/neu protein. However, it is not without risks. In rare cases, deaths due to heart and lung problems have been linked to its use.
Study selection criteria: Phase II and III clinical trials with 100 or more participants with HER2/neu-positive metastatic breast cancer.
Study
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Study Population
(number of participants)
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Percent who had Previous Chemotherapy for Metastatic Breast Cancer
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Drug(s) Used
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Overall Response Rate—Percent who Responded to Treatment
(95% CI)
|
Rate of Death at One Year
(phase III trials only)
|
Phase III clinical trials
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Slamon et al. [1]
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235
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0%
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Trastuzumab plus chemotherapy
(anthracycline & cyclophosphamide; or paclitaxel)
|
50%Sig
(44-57%)
|
22%Sig
|
| |
|
|
Chemotherapy alone (anthracycline and cyclophosphamide; or paclitaxel)
|
32%
(26-38%)
|
33%
|
Robert et al. [2]
|
196
|
47%
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Trastuzumab with chemotherapy (paclitaxel)
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36%
(26-46%)
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13%*
|
| |
|
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Trastuzumab with chemotherapy (paclitaxel plus carboplatin)
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52%
(41-62%)
|
10%*
|
Tripathy et al. [3]
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154 women who progressed on chemotherapy alone
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100%
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Trastuzumab with chemotherapy (paclitaxel; vinorelbine; docetaxel; fluorouracil; cyclophosphamide; cisplastin; docorubicin; gemcitabine)
|
14%
(8.3-19.2%)
|
N/A
|
| |
93 women who progressed on chemotherapy and trastuzumab
|
100%
|
Trastuzumab with chemotherapy (paclitaxel; vinorelbine; docetaxel; fluorouracil; cyclophosphamide; cisplastin; docorubicin; gemcitabine)
|
11%
(4.5-17.0%)
|
N/A
|
Seidman et al. [4]
|
178
|
54%
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Trastuzumab with chemotherapy (paclitaxel)
|
Paclitaxel weekly:
55%
(45-65%)
Paclitaxel every 3 weeks:
58%
(46-69%)
|
N/A
|
Phase II clinical trials
|
Cobleigh et al. [5]
|
222
|
100%
|
Trastuzumab alone
|
15%
(11-21%)
|
|
Marty et al. [6]
|
186
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0%
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Trastuzumab with chemotherapy (docetaxel)
|
61%
(50-71%)
|
|
Vogel et al. [7]
|
114
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0%
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Trastuzumab alone
|
26%
(18.2-34.4%)
|
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Baselga et al. [8]
|
105
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0%
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Trastuzumab alone
|
19%
(12-28%)
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CI=Confidence interval.
Sig=Statistically significant improvement compared to chemotherapy alone.
N/A=Not applicable.
*Approximate mortality rates at one year of follow-up. Estimated 4-year survival was 29% for trastuzumab + paclitaxel and 39% for trastuzumab + paclitaxel + carboplatin.
References
1. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of Chemotherapy Plus a Monoclonal Antibody Against HER2 for Metastatic Breast Cancer that Overexpresses HER2. N Engl J Med. 344(11):783-92, 2001.
2. Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 24(18):2786-92, 2006.
3. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol. 22(6):1063-70, 2004.
4. Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 26(10):1642-9, 2008.
5. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 17:2639-48, 1999.
6. Marty M, Cognetti F, Maraninchi D, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 23(19):4265-74, 2005.
7. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 20(3):719-26, 2002.
8. Baselga J, Carbonell X, Castaneda-Soto NJ et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol. 23(10):2162-71, 2005.
Updated 03/12/10
