The study reviewed here suggests that an experimental chemotherapy medicine called eribulin may be a good treatment option for metastatic breast cancer that has stopped responding or failed to respond to other treatments.
The results were presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting.
Eribulin is made from a sea sponge. Like some other chemotherapy medicines, eribulin works by interfering with microtubulin, a component of cells. When both healthy and cancer cells divide, microtubulin acts as a building block for the structures that make sure the cell reproduces. Microtubulin also helps sort genetic material in the cell during cell division. So interfering with microtubulin can disrupt cell division and make cancer cells die.
The EMBRACE trial looked at 762 women diagnosed with metastatic breast cancer who had been treated previously with two to five other chemotherapy medicines; some of the women also had received hormonal therapy or a targeted therapy.
The women were split into three different treatment groups that got either:
Compared to women who got supportive care or a standard metastatic cancer treatment, the women who got eribulin:
Better overall survival is important because several other new treatments have improved the length of time before the cancer starts growing again, but not overall survival. Still, the number of women who responded to eribulin (12.2%) is low. That response rate was better than the 4.7% response rate for women who got a standard treatment, but the low response rate to eribulin shows how challenging it is to treat metastatic breast cancer that has stopped responding to standard treatments.
Side effects caused by eribulin were similar to side effects caused by other chemotherapy medicines, including hair loss, neuropathy, low white blood cell counts, and fever. About 25% of women in both the eribulin group and the standard treatment group had to lower their dosage or stop treatment because of serious side effects or complications.
This study suggests that eribulin might be a good option to treat advanced-stage breast cancer that has stopped responding to other treatments. Researchers also may study eribulin as a treatment for less-advanced breast cancer.
If you're being treated for advanced-stage breast cancer, you and your doctor may be considering a number of treatment options, especially if the cancer has stopped responding to standard treatments. If you're willing to participate in a clinical trial, you may have even more options available, possibly including an experimental treatment such as eribulin. Talk to your doctor about clinical trials that might be a good fit for you and your unique situation. Visit the Breastcancer.org Clinical Trials pages for more information.
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CHICAGO (MedPage Today) -- Eribulin, a novel chemotherapy drug derived from a sea sponge, improves survival in heavily-pretreated metastatic breast cancer, researchers found.
Median survival rose to 13.12 months with eribulin compared with 10.65 months on physicians' choice of other chemotherapeutic, biologic, or endocrine therapy (P=0.04), Christopher Twelves, MBChB, PhD, of the University of Leeds and St. James' University Hospital in Leeds, England, reported here at the American Society of Clinical Oncology meeting.
Over the past 25 years, only a handful of drugs of any type have been shown to improve overall survival in metastatic breast cancer, Twelves said at a press conference where the results were presented.
"Eribulin is actually the only single agent -- be that chemotherapy, biologic therapy, or endocrine therapy -- that has shown overall survival in such heavily pretreated women with metastatic breast cancer," he noted.
William J. Gradishar, MD, of Northwestern University in Chicago, was impressed by 23% overall survival advantage with eribulin, saying that another treatment option would be useful in this setting.
This nearly 2.5-month survival advantage likely will be enough to get the drug approved in the refractory metastatic setting, commented press conference moderator Eric P. Winer, MD, of the Dana-Farber Cancer Institute in Boston.
Former member of the FDA's Oncologic Drugs Advisory Committee Joanne E. Mortimer, MD, of the City of Hope Cancer Center in Duarte, Calif., agreed that this effect would probably be sufficient for the FDA, though its reviewers will be taking a careful look at the adverse events.
Eribulin represents a new class of microtubulin inhibitors, which Twelves described as attacking the scaffolding by which cells divide but at a different point than the taxanes, vinca alkyloids, and other existing microtubulin inhibitors.
In the open-label phase III EMBRACE trial, the researchers compared this agent, at a dose of 1.4 mg/m2 given intravenously over two to five minutes on days 1 and 8 of every 21-day cycle, to the physicians' choice (set beforehand) of any approved single-agent cytotoxic, hormonal, or biologic therapy or supportive care alone.
"We don't have a strong evidence base to suggest which, if any, is appropriate," Twelves said at the press conference.
The study included 762 women with locally recurrent or metastatic breast cancer who were heavily pretreated with two to five prior chemotherapies including prior taxane and anthracycline.
For the primary endpoint, the researchers reported a 19% reduction in the risk of death (HR 0.81, 95% confidence interval 0.66 to 0.99).
The researchers also reported a significant benefit in progression-free survival (3.7 versus 2.2 months) and a higher overall response rate (12.2% versus 4.7%) with the new chemotherapy drug.
While encouraging that this response was was substantially higher with the novel agent, the rate remained low in both groups, indicating how poorly sensitive these heavily pretreated patients are, commented Steven J. Isakoff, MD, PhD, of Massachusetts General Hospital in Boston, who wasn't involved in the study.
These results came with a "manageable" safety profile, which came with excess grade 3 or 4 febrile neutropenia (4.2% versus 1.2%), neuropathy (8.2% versus 2.0%), and some hair loss, Twelves said.
Overall, though, grade 3 or 4 side effects that required dose adjustment or temporary or permanent drug discontinuation occurred at the same level for eribulin and physician-chosen single-agent therapies (25.0% versus 25.9%).
Twelves pointed out that only 4.8% of the eribulin group actually had to stop treatment.
One puzzling result was that the duration of response among those who achieved tumor shrinkage actually favored the routine clinical choices of therapy compared with the new cytotoxic (4.1 versus 6.7 months).
Twelves cautioned against overinterpreting this result, given that it was based upon only about 10 patients.
Gradishar agreed that, while counterintuitive, "at the end of the day survival is what matters."
The positive results may also suggest trying the drug in earlier stages of the disease, as has been the model for development of other chemotherapeutic agents, Twelves said.
Combinations with targeted agents are also warranted, Winer noted.
"This is the era of targeted therapy, it's not the era of chemotherapy in general," he said at the press conference. "I don't know that there are going to be many more chemotherapeutic agents approved for women with breast cancer. We have a number and we probably have a sufficient number to combine with other agents. This may be one of the last."
The study was sponsored by Eisai.
Twelves reported having served in a consultant or advisory role and expert witness for Eisai.
Coauthors also reported conflicts of interest with Eisai as well as with BMSO and ImClone Systems.
Winer reported conflicts of interest with Genentech. Gradishar reported no conflicts of interest. Isakoff reported no personal financial conflicts of interest, though he has received research funding from many pharmaceutical companies involved in breast cancer treatment without personal renumeration.
Primary source: American Society of Clinical Oncology meeting Source reference: Twelves C, et al "A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane" ASCO 2010; Abstract CRA 1004.
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