June 8, 2010 (Chicago, Illinois) — A new chemotherapy agent has shown a significant survival benefit in heavily pretreated breast cancer, the first time that such an improvement has been seen in this patient population.
The new drug, eribulin (developed by Eisai), is not available yet, but these data — from a phase 3 registration trial known as EMBRACE — stirred up quite a bit of excitement among breast cancer specialists here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.
It will be a most welcome addition to our armamentarium.
"It will be a most welcome addition to our armamentarium for metastatic breast cancer," said Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, who acted as discussant for this study.
|Dr. Christopher Twelves|
On the basis of these data, eribulin is awaiting approval in the United States, Europe, and Japan. In the United States, it has been designated priority review by the US Food and Drug Administration; a decision is expected in September 2010.
The drug is a novel chemotherapy based on a compound extracted from a sea sponge, and represents a new chemical class of halichondrins. It targets microtubules, but in a different way than existing agents, explained Christopher Twelves, MD, from the University of Leeds, United Kingdom, who presented the findings.
Real-Life Design of Study
The phase 3 clinical trial involved 762 patients with metastatic breast cancer who had been heavily pretreated with previous chemotherapy regimens (median of 4) that had to have included an anthracycline and a taxane.
These women were randomized in a 2:1 fashion to eribulin or a treatment of physician's choice (TPC), where the oncologist decided which drug to use. Many chose to use vinorelbine, gemcitabine, or capcitebine, and none chose best supportive care, although this was an option, Dr. Twelves explained.
In response to a question about the design of this study, Dr. Twelves said it represented a "real-life situation. If we had mandated what drug to use, colleagues would have said that the results are not applicable because that is not how they treat their patients."
Dr. Burstein agreed that this represented a real-life situation because there is no clear option of what drug to use next. "Beyond third line, there are no data to suggest that there is a benefit," he said.
The results show that overall survival was significantly better with eribulin than with TPC (13.12 vs 10.65 months, a difference of 2.47 months; hazard ratio, 0.81; P = .041). The 1-year survival was 53.9% with eribulin and 43.7% with TPC.
"This is clinically relevant in this patient population," Dr. Twelves noted.
"Over the past 5 years in metastatic breast cancer, no trial with overall survival as an end point has shown an improvement, so I think this is a striking finding," he said. The last trial to find an increase in overall survival in metastatic breast cancer was docetaxel. That was more than 10 years ago, and was not in such heavily pretreated patients, he added.
The secondary end point of progression-free survival met statistical significance only when the investigator's assessment was used, not on independent review, and Dr. Twelves said this might represent differences in how progression was measured.
Dr. Burstein wondered why progression-free survival was out of proportion with the improvement in overall survival that was seen, and he noted that the response rate to the new drug, although significant (12.2% with eribulin vs 4.7% with TPC; P = .002), was on the low side.
Adverse effects overall were similar to those seen in the TPC group, Dr. Twelves reported. Comparison of specific adverse effects is difficult because of the many different drugs used in that group, but eribulin was associated with more neutropenia (grade 3 in 3% of patients vs 0.8% for TPC) and neuropathy (grade 3 in 7.8% of patients vs 2% for TPC).
"I would say that this is acceptable to me for women with metastatic breast cancer," Dr. Burstein said.
"This trial provides high-level evidence for outcomes in heavily pretreated metastatic breast cancer," Dr. Burstein concluded.
It potentially establishes a new option for women with heavily pretreated breast cancer.
"It potentially establishes a new option for women with heavily pretreated breast cancer; up to now, we haven't had a clear idea of what to use for them," Dr. Twelves explained.
At an ASCO press conference at which these results were highlighted, moderator Eric Winer, MD, professor of medicine at Harvard Medical School in Boston, was asked to speculate on whether these data are sufficient for approval of the drug. While pointing out that this is a decision for the regulatory authorities, he believes there is a "reasonable chance" because this was a positive study showing a survival benefit in a patient population where there is no clear choice of therapy.
Dr. Winer added that in this era of targeted therapy, he is not sure that there are going to be many more chemotherapy agents that are approved; eribulin may be one of the last.
Dr. Twelves reports acting in a consultancy and advisory role and providing expert testimony for Eisai. Dr. Burstein has disclosed no relevant financial relationships. Dr. Winer reports employment or leadership with Susan G. Komen for the Cure, acting in a consultancy or advisory role for Eisai (uncompensated), Pfizer, and Roche/Genentech (uncompensated), and receiving research funding from Genentech, Stand Up to Cancer, and Susan G. Komen for the Cure.
American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA1004^. Presented June 8, 2010.
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Cite this: Eribulin Offers New Option in Heavily Pretreated Metastatic Breast Cancer - Medscape - Jun 08, 2010.