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Bevacizumab Studies Show Benefit in Early Breast Cancer

Report on effectiveness of bevacizumab added to chemotherapy for HER2 negative breast cancer that has not metastisized

March 9, 2012

Written By Michael J. Formica, MS, MA, EdM
Reviewed By Hope S. Rugo, MD

Results from two studies show adding bevacizumab (Avastin) to docetaxel-based chemotherapy before surgery improves the rate of pathologic complete response in HER2 negative breast cancer that has not metastasized, or traveled to other parts of the body. Pathological complete response (pCR) means there is no evidence of invasive cancer after treatment.

Both studies were published in the New England Journal of Medicine. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-40 trial was conducted in the United States and the GeparQuinto (GBG44) trial in Germany. Both found a statistically significant increase in pCR for women treated with this combination, meaning it was unlikely to have happened by chance.

Background and Reason for the Study

These studies were begun after the U.S. Food and Drug Administration granted accelerated approval in 2008 for bevacizumab in metastatic HER2 negative breast cancer. In 2011, FDA withdrew approval because an independent review found bevacizumab’s side effects outweighed its benefits. In tests of bevacizumab added to chemotherapy for metastatic breast cancer, increases in progression-free survival, the length of time after treatment begins that the breast cancer does not grow, did not carry over to increases in overall survival, the time from start of treatment until death from any cause.

Bevacizumab remains available through clinical trials or off-label (for unapproved use), and it is still approved in Europe for advanced breast cancer treatment. (For more background, enter “Avastin” in the search box on the upper right.)

In the current studies, researchers looked at the impact of bevacizumab on pCR in early-stage breast cancer.

Structure of the Studies

Both trials were phase III, comparing new treatments to standard treatments. NSABP B-40 defined pCR as no cancer in the breast after treatment. GBG44 defined it as no cancer in the breast and axillary, or underarm, lymph nodes.

NSABP B-40 researchers assigned 1,206 women with stage I, II or IIIA breast cancer to receive docetaxel (Taxotere), docetaxel with capecitabine (Xeloda) or docetaxel with gemcitabine, four times once every three weeks. This was followed by doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), again four times once every three weeks. Over the first six of these cycles, the participants were treated with or without bevacizumab.

In the GBG44 trial, 1,948 women with untreated HER2 negative breast cancer with cancer in the lymph nodes were randomly assigned to get epirubicin (Ellence) and cyclophosphamide followed by docetaxel, with or without bevacizumab.

Results of the Studies

In the NSABP B-40 trial, adding capecitabine or gemcitabine to docetaxel prompted no significant increase in pCR, compared to docetaxel alone. Adding bevacizumab increased pCR 6.3 percent, which was statistically significant.

The GBG44 study showed a significant 3.5 percent increase in pCR with bevacizumab. Women in this trial with triple-negative breast cancer got greater benefit, with a significant 11.4 percent improvement in pCR. In the NSABP B40 trial, the benefit was limited to women whose cancers were hormone receptor positive.

Bevacizumab has some serious side effects, including severe stomach problems, bleeding, blood clots and high blood pressure that can lead to stroke.

The results of these studies do not resolve concerns about bevacizumab that prompted FDA’s withdrawal of its approval as a breast cancer medicine.

What This Means for You

If you are being treated for non-metastatic HER2 negative breast cancer, you and your care team are likely considering several treatment options. Clinical trials may give you more options, including treatment with medicines like bevacizumab that are not available elsewhere. If you feel comfortable participating in a clinical trial, talk with your care team. You can also read LBBC’s Guide to Understanding Breast Cancer Treatment Research Studies for more information.

Learn more about GBG44 and NSABP B-40.

von Minckwitz, G., et. al., Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer. The New England Journal of Medicine, January 2012; 366:299-309

Bear, H., et. al., Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer. The New England Journal of Medicine, January 2012; 366:310-320