Bevacizumab Combined With Chemotherapy Improves Progression-Free Survival for Patients With Advanced Breast Cancer
Preliminary results from a large, randomized clinical trial for
patients with previously untreated recurrent or metastatic breast
cancer cancer that has spread from the breast to other parts
of the body show that those patients who received bevacizumab
(Avastin) in combination with standard chemotherapy had
a longer time period before their cancer progressed than patients
who received the same chemotherapy without bevacizumab.
The clinical trial was sponsored by the National Cancer Institute
(NCI), part of the National Institutes of Health, and conducted
by a network of researchers led by the Eastern Cooperative Oncology
Group (ECOG). Genentech, Inc., South San Francisco, Calif., which
manufactures bevacizumab, provided bevacizumab for the trial under
the Cooperative Research and Development Agreement (CRADA) with
NCI for the clinical development of bevacizumab.
The Data Monitoring Committee overseeing the trial (known as E2100)*
recommended that the results of a recent interim analysis be made
public because the study had met its primary endpoint of increasing
progression-free survival (the amount of time patients lived without
the cancer getting worse).
Preliminary results suggest that patients in the study who received
bevacizumab in combination with standard chemotherapy consisting
of single-agent paclitaxel had a delay in worsening of their cancer
by four months, on average, compared to patients treated with paclitaxel
chemotherapy alone. This difference is statistically significant.
“This study is the first to find a benefit of anti-angiogenic therapy
in patients with breast cancer and represents a major advance in
the treatment of patients with metastatic disease," said Study
Chair Kathy D. Miller, M.D., of the Indiana University Medical
Center in Indianapolis, Ind. Anti-angiogenic drugs, also called
angiogenesis inhibitors, are substances that may prevent angiogenesis,
or the formation of blood vessels. In anticancer therapy, an angiogenesis
inhibitor prevents the growth of blood vessels from surrounding
tissue to a solid tumor.
“Recent clinical trials have shown that anti-angiogenic drugs have
a favorable impact on colon and lung cancers,” said NCI Director
Andrew C. von Eschenbach, M.D. “This study demonstrates that
when patients with recurrent or metastatic breast cancer received
bevacizumab in addition to their chemotherapy, the period of time
that they lived with their cancer under control was increased.
This is an important step in our journey to ultimately eliminate
the suffering and death due to cancer.”
A total of 722 women with recurrent or metastatic breast cancer
who had not previously received systemic chemotherapy for their
recurrent or metastatic disease were enrolled in this study between
December 2001 and May 2004. Patients were randomized to one of
the two treatment arms. One patient group received standard treatment
consisting of single-agent paclitaxel. The second group received
the same regimen of paclitaxel with the addition of bevacizumab.
Patients whose tumors overexpressed HER-2 were not included in
the study unless they had previously received trastuzumab (Herceptin)
or were unable to receive trastuzumab. Also excluded were patients
who had received preventive chemotherapy treatment with paclitaxel
within the previous 12 months, as well as patients with a prior
history of blood clots or who were on blood thinners. Serious bleeding
and blood clots were rare in this study. Patients receiving the
combination of paclitaxel and bevacizumab had slightly more neuropathy,
or problem in peripheral nerve function (any part of the nervous
system except the brain and spinal cord); abnormally high blood
pressure; and proteinuria, a condition in which urine contains
an abnormal amount of protein, than patients receiving paclitaxel
alone. Other side effects were similar between the two treatment
groups.
Bevacizumab, a humanized monoclonal antibody** that already has
been approved for metastatic colorectal cancer in combination with
chemotherapy, is designed to bind to and inhibit vascular endothelial
growth factor (VEGF). VEGF is a protein that plays a critical role
in tumor angiogenesis.
“It is noteworthy that a previous company-sponsored trial in patients
who received prior chemotherapy for advanced disease did not show
a benefit with bevacizumab in combination with capecitabine, a
different chemotherapy agent,” said JoAnne Zujewski, M.D.,
who heads breast cancer trials for NCI’s Cancer Therapy Evaluation
Program. “It is fortunate that ECOG, assisted by multiple
other NCI-sponsored Cooperative Groups, persisted with this trial
in patients with newly diagnosed advanced breast cancer, as the
agent is clearly active in this setting.”
An estimated 211,240 women will be diagnosed with breast cancer
in the United States in 2005. Breast cancer is the most commonly
diagnosed cancer in women and the second leading cause of cancer-related
death in women in this country. An estimated 40,110 deaths from
female breast cancer will occur in 2005 in the United States, accounting
for about 15 percent of all cancer-related deaths in women in the
nation.
For more information about cancer, please visit the NCI Web site
at http://www.cancer.gov or call NCI's Cancer Information Service
at 1-800-4 CANCER (1-800-422-6237).
* E2100: A randomized phase II/III trial of paclitaxel versus paclitaxel
plus bevacizumab as first-line therapy for locally recurrent or metastatic
breast cancer.
** Monoclonal antibodies are laboratory-produced
substances that can locate and bind to specific substances in the body. “Humanized” monoclonal
antibodies include some sequences that are the same as those in human
antibodies in order to avoid being destroyed by the patient’s own
immune system.
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