In November, following an emotional public hearing some months earlier, the
Now, confusingly, Avastin is back in the news again — this time, with positive results in two early trials of women with early-stage breast cancer whose tumors have not traveled beyond the breast or nearby
The results are suggestive, but not conclusive, says Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. "This is not the kind of study that will have doctors changing their practice tomorrow. It's going to take some time to sort out."
Here's a closer look at Avastin, its track record and its potential.
The drug is an antibody that binds and inactivates a naturally occurring substance — vascular endothelial growth factor — that helps the body form new
The drug was a potentially game-changing treatment when it was first approved by the FDA in 2004, for
It was approved via an accelerated process in 2008 for metastatic breast cancer after early positive results in such patients indicated it seemed to halt tumor growth. But as patients were tracked for longer periods of time, it became clear that they weren't living any longer. Additional studies confirmed the lack of any survival edge and revealed far more about the side effects. The drug seems to worsen some side effects of chemotherapeutic drugs given with it and also increased risk of severe
In July 2010, after reviewing all the evidence, an FDA advisory committee voted, 12-1, to withdraw the drug for breast cancer treatment, concluding that the benefits did not outweigh the risks. The agency gave the public and the drug's maker,
And now, the new studies. How do they fit in?
Published last week in the New England Journal of Medicine, both tested whether Avastin, in combination with chemotherapeutic drugs, would help shrink tumors before surgery. This strategy is called neoadjuvant therapy, and in many cases it has allowed doctors to reduce the extent of surgery, says Dr. Helena Chang, a surgical
The first study, done in
Patients then had surgery to remove tissue from the breast site where tumors had been detected as well as the lymph nodes that had cancer in them. Their tissue was assessed microscopically to search for cancer cells.
Researchers reported that 18.4% of patients receiving Avastin responded completely to neoadjuvant therapy — they had "not a single tumor cell left," says study coauthor Dr. Gunter von Minckwitz, a researcher with the German Breast Group in Neu-Isenburg. In the group that did not get Avastin, 14.9% of patients had a complete response.
The second study, done in the U.S., studied 1,206 patients, again with HER2-receptor-negative breast cancer. Various combinations of chemotherapy drugs were tested with or without Avastin. Results showed 34.5% of patients with Avastin responded completely to the neoadjuvant therapy compared with 28.2% who did not receive it.
The results in both studies were statistically significant but quite small — the percent of patients helped by Avastin increased by 4 percentage points in Germany and 6 in the U.S.
Still, these results, along with others yet to come, "may show us that there's a place for this drug" in treating early breast cancer cases, says U.S. study coauthor Dr. Harry Bear, a surgical oncologist at
But it's too soon to tell: These studies only focus on pathology results. They haven't followed patients long enough to see how diseases progress and whether the drug offers any survival edge. To that end, both research groups plan to follow their subjects for at least five years.
There are some confusing things about the two studies in identifying which patients might best respond to the Avastin.
In the U.S. study, the positive effects of Avastin were detected only in a subgroup of patients with so-called hormone-sensitive tumors, which grow when exposed to estrogen or progesterone. But in the German study, the opposite was true — statistically positive effects were seen only when looking at the hormone-insensitive subgroup. That might mean that hormone-sensitivity is irrelevant to the response to Avastin and the results just fell out that way by chance.
Researchers hope that preserved tissue samples from both studies may reveal other characteristics of cancers that can help predict which patients are most likely to benefit from Avastin.
Researchers took steps to manage the known cardiovascular side effects, screening study subjects for cardiac function before enrolling them and monitoring blood pressure throughout the study.
Both studies, however, reported increased rates of neutropenia with fever (a low white blood cell count that diminishes the body's response to infection), mucositis (sores and sensitivity of the mucous membranes lining the
For now, doctors will see no change in their practice.
Chang says she is encouraged by the results but is not ready to recommend Avastin to her patients. "I want more evidence," she says.
"What we really need is a test that tells us which women are most likely to benefit, because there's significant cost, in dollars and in side effects and risks," Lichtenfeld says.