Among women with HER2-negative breast cancer that has not spread to distant sites in the body, the addition of Avastin to neoadjuvant (before-surgery) chemotherapy may increase the likelihood of a complete response to treatment (a disappearance of detectable cancer). These results were published in the New England Journal of Medicine.
Avastin is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin is used in the treatment of several types of cancer, but its approval for breast cancer was revoked by the US Food and Drug Administration (FDA) in November, 2011.
Avastin was originally for breast cancer in 2008 under the FDA’s accelerated approval program. The accelerated approval program provides earlier access to promising drugs for life-threatening health conditions while confirmatory studies are conducted. The approval was for use of Avastin in combination with chemotherapy for women with metastatic, HER2-negative breast cancer. The approval was based on the finding that Avastin delayed the progression (worsening) of metastatic breast cancer. There was no evidence that Avastin improved overall survival.
After 2008, additional studies were reported to the FDA. These studies found that Avastin had only a small effect on rate of cancer progression and no effect on overall survival. The FDA concluded that the potential benefits of Avastin for breast cancer did not outweigh the risks, and revoked Avastin’s approval for breast cancer. Risks of Avastin include severe high blood pressure; bleeding problems; the development of perforations (holes) in the nose, stomach, and intestines; and heart attack or heart failure. It remains possible that Avastin will be found to benefit specific subgroups of breast cancer patients, and the FDA noted that it is open to considering data from additional studies that address this question.
Results from Avastin clinical trials continue to be reported. Two of these were published in the New England Journal of Medicine and address the use of Avastin in women with earlier-stage (nonmetastatic), HER2-negative breast cancer.
The first study—the Phase III GeparQuinto trial—enrolled 1,948 women with nonmetastatic, HER2-negative breast cancer. Study participants received neoadjuvant treatment with chemotherapy alone or in combination with Avastin. The primary outcome of interest was a complete response, which was defined in this study as no detectable cancer in the breast or axillary (under-the-arm) lymph nodes.
- A complete response to treatment occurred in 14.9 percent of women treated with chemotherapy alone and 18.4 percent of women treated with chemotherapy plus Avastin.
- The greatest benefit of Avastin was observed among women with triple-negative breast cancer (breast cancer that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative). Among these women, the complete response rates were 27.9 percent with chemotherapy alone and 39.3 percent with chemotherapy plus Avastin.
- Serious side effects that were more common in the Avastin group included febrile neutropenia (low white-blood cell counts accompanied by fever), mouth sores, hand-foot syndrome, infection, and high blood pressure.
The second study—the Phase III NSABP B-40 trial—involved 1,206 women with nonmetastatic, HER2-negative breast cancer. Once again, study participants received neoadjuvant treatment with chemotherapy alone or in combination with Avastin. In this study, a complete response was defined as no detectable cancer in the breast; this is a less stringent definition than was used by the GeparQuinto study, which required no detectable cancer in the breast or axillary lymph nodes.
- A complete response to treatment occurred in 28.2 percent of women treated with chemotherapy alone and 34.5 percent of women treated with chemotherapy plus Avastin.
- When a more stringent definition of complete response was used (similar to what was used in the GeparQuinto study), the difference between study groups was not statistically significant, suggesting that it could have occurred by chance alone.
- The greatest benefit of Avastin was observed among women with estrogen receptor-positive cancer. This differs from what was found in the GeparQuinto study.
- Side effects that were more common in the Avastin group included high blood pressure, heart problems, hand-foot syndrome, and mouth sores.
These results suggest that the addition of Avastin to neoadjuvant chemotherapy may increase the likelihood of a complete response among women with nonmetastatic, HER2-negative breast cancer. Whether this will ultimately translate into improved survival, however, remains uncertain. Overall survival results are not yet available from these studies. The question of whether certain subgroups of patients are more likely to benefit from Avastin than others also remains unanswered, but research is ongoing.
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