January 25, 2011— -- Taking Avastin before breast cancer surgery could significantly shrink tumors and reduce the chance of recurrence in women with less common but more aggressive forms of breast cancer, according to two new studies. The U.S. Food and Drug Administration revoked approval of Avastin for late-staged breast cancer treatment last November.
But the two studies, published Wednesday in the New England Journal of Medicine, suggest the drug could work for women with earlier stages of breast cancer before undergoing surgery.
The first study, undertaken in Europe, found that patients with triple negative breast cancer who received Avastin along with standard therapy had an 11 percent greater chance of having their tumor completely disappear compared with those who did not receive Avastin.
An estimated 10 to 17 percent of breast cancers are considered triple negative, according to the American Cancer Society. This aggressive type of cancer is less responsive to hormone therapy.
The second study, which was done in North America, found that the same type of patients as in the European study who were on Avastin were 6 percent more likely to have their tumor completely disappear compared with those who did not receive Avastin. But, unlike the first study, the greatest benefit of all was found in women with a less aggressive form of breast cancer.
While many experts said the findings suggested that Avastin had some role in treating some forms of breast cancer for some women, it wasn't clear what its role should be.
While many experts said the findings suggested that Avastin might stop some tumors from growing, and eliminated some completely, the findings led to more questions than answers
"There is a small benefit, but how much does a 5 to 10 percent increase in tumor disappearance really mean if it does not improve survival and leads to toxicity," said Dr. Charles Shapiro, director of Breast Medical Oncology at the Ohio State University Comprehensive Cancer Center.
The FDA revoked its approval of Avastin for use in metastatic breast cancer patients in November 2011, citing a lack of evidence on what type of patients would benefit and that the benefits of the drug outweigh the risks.
"I still don't believe there's a clear message from these studies as to who would benefit and how the medication should be used," said Dr. Len Lichtenfeld, deputy chief medical officer at the American Cancer Society.
Some patients who were put on Avastin during the trial experienced skin infections, high blood pressure and mild heart failure – the same side effects that called the drug into question during the FDA's review.
The federal agency granted an accelerated conditional approval for Avastin in February 2008 to treat late-stage breast cancer patients. It had been suggested that the drug slowed the progression of the disease and improved overall survival. But results from four trials that enrolled more than 3,000 women found no significant reduction in progression of the disease or improvement of death rates among those who took Avastin and underwent chemotherapy.
Doctors had previously reported seeing their patients benefit by taking Avastin, but it's not clear which patients it helps the most.
"Frankly, what would help in further understanding Avastin are predictive tests on what type of women would benefit," said Lichtenfeld.
The additional studies, carried out by Avastin maker Genentech, found only a small effect on tumor growth and no evidence that patients lived longer than they would have undergoing standard chemotherapy.
Still, the studies released Wednesday add to the growing research in so-called neoadjuvant therapies, the concept of giving heavy-hitting medications to early stage patients before surgery to shrink the tumor and stop its progression.
"The strategy is proving to be an important strategy," said Dr. Joseph Sparano, director of Breast Medical Oncology at Montefiore Medical Center in Bronx, N.Y.
Studies released earlier this month found therapy agents such as Tykerb or Herceptin -- typically used for later stages of the disease when the tumor is considered inoperable -- downsized the tumor enough to perform surgery for women with HER2 positive breast cancer.
The current studies are among the first to suggest Avastin may benefit patients with triple negative breast cancer before surgery. But longer term studies may offer a better idea of how long a patient will survive post-surgery without disease, experts said.
"This is really a fascinating development. It will force us to reassess the criteria for advancing new drugs," said Dr. David Euhus, chairman in breast cancer surgery at the University of Texas Southwestern Medical Center in Dallas. "It may also give [Avastin] a second chance in breast cancer."