Eribulin Survival Benefit in Metastatic Breast Cancer: Data Published
March 3, 2011 — For the first time, a single agent has shown a significant improvement in survival in women with heavily pretreated metastatic breast cancer. That finding for eribulin (Halaven, Eisai) comes from the pivotal phase 3 EMBRACE trial.
These data were reported at last year's annual meeting of the American Society of Clinical Oncology (ASCO), where they stirred up quite a bit of excitement among breast cancer specialists, and they led to the approval of eribulin by the US Food and Drug Administration in November 2010.
The EMBRACE results were published online today in the Lancet. The researchers, headed by Javier Cortes, MD, from the Vall d'Hebron University Hospital, in Barcelona, Spain, conclude that "eribulin showed a significant and clinically meaningful improvement in overall survival compared with treatment of physicians' choice [TPC] in women with heavily pretreated metastatic breast cancer."
"Our demonstration of improved overall survival as the primary end point in women with metastatic breast cancer treated with cytotoxic therapy seems unique, and challenges the idea that such an expectation is unreasonable," they write.
"This global phase 3 study establishes a new standard treatment for women with heavily pretreated metastatic breast cancer, for whom there was previously no chemotherapy treatment with proven survival benefit," they add.
Real-World Comparison
Participants in this study had already received 2 to 5 chemotherapy regimens (median, 4; range, 1 to 7), including an anthracycline and a taxane.
They were randomized in a 2:1 ratio to receive either eribulin (1.4 mg/m2 intravenously for 2 to 5 minutes on days 1 to 8 of a 21-day cycle) or TPC. This was defined as any single-agent treatment (chemotherapy, hormonal or biological) or radiotherapy or symptomatic therapy alone. Many physicians chose to use vinorelbine, gemcitabine, or capecitabine, and none chose best supportive care, even though this was an option, said coauthor Christopher Twelves, MD, from the University of Leeds, United Kingdom, when he presented this trial at the ASCO meeting last year.
This represents "a real-life situation," he noted, because there are no guidelines on which chemotherapy to use after third-line therapy.
At the time, the discussant of the paper, Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, agreed with that description. He makes the same point in an editorial accompanying the study, which he coauthored with his Dana-Farber colleague Nancy Lin, MD.
"Ultimately, the EMBRACE study invited a real-world comparison of best clinical guess versus eribulin," the editorialists write.
The use of TPC is an important strength of this study, say the trialists. Because the results reflect real-life choices made by oncologists and their patients, the benefits of eribulin seen in this trial are "arguably more likely to be generalizable to clinical practice than if the control treatment had been artificially constrained," they write in the paper.
Is Survival Benefit Clinically Meaningful?
The difference between overall survival in the 2 treatment groups was statistically significant; median overall survival was 13.1 months with eribulin and 10.6 months with TPC (hazard ratio, 0.81; P = .041).
This survival benefit is "clinically meaningful," say the trialists, because the median survival benefit of 2.5 months represents an increase of 23% for these women.
This is similar to what has been reported for docetaxel vs mitomycin plus vinblastine (31%), and for capecitabine plus docetaxel vs docetaxel alone (26%).
In addition, they point out that the survival benefit with eribulin was achieved "with a manageable profile of toxic effects." The most common adverse events were asthenia and fatigue (reported by 54% of patients in the eribulin group and 40% in the TPC group) and neutropenia (52% vs 30%). The most common adverse event leading to the discontinuation of eribulin was peripheral neuropathy, occurring in 5% of patients.
However, the editorialists point out that the survival benefit can be measured in weeks, and say that "it is fair to ask whether there is clinical significance."
The outcomes for the TPC group provide "a sobering reminder of the modest results in the nth-line therapy of breast cancer," Dr. Lin and Dr. Burstein note.
Most oncologists participating in a recent survey (Eur J Cancer. 2010;8:77 [abstract 63]) said that they consider prolongation of life by 2 to 6 months to be a "meaningful incremental gain." However, the same survey found that most patients believe that a threshold of 10 months or more is needed to warrant treatment, the editorialists note.
"But surely some survival benefit is better than none at all," they add.
The data from the EMBRACE trial provide "much needed high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," the editorialists write. "And that evidence suggests that the methods to treat advanced breast cancer are growing, the treatment challenge in refractory disease is a little bit less daunting, and the treatment results are a little bit better than they were before."
The EMBRACE study was funded by Eisai. Several of the study authors report receiving consultancy fees, honoraria, and/or grants from Eisai, as well as from several other pharmaceutical companies; full details are given in the paper. Dr. Lin and Dr. Burstein have disclosed no relevant financial relationships.
http://spaineldorado.blogspot.com/2011/03/eribulin-survival-benefit-in-metastatic.html
These data were reported at last year's annual meeting of the American Society of Clinical Oncology (ASCO), where they stirred up quite a bit of excitement among breast cancer specialists, and they led to the approval of eribulin by the US Food and Drug Administration in November 2010.
The EMBRACE results were published online today in the Lancet. The researchers, headed by Javier Cortes, MD, from the Vall d'Hebron University Hospital, in Barcelona, Spain, conclude that "eribulin showed a significant and clinically meaningful improvement in overall survival compared with treatment of physicians' choice [TPC] in women with heavily pretreated metastatic breast cancer."
"Our demonstration of improved overall survival as the primary end point in women with metastatic breast cancer treated with cytotoxic therapy seems unique, and challenges the idea that such an expectation is unreasonable," they write.
"This global phase 3 study establishes a new standard treatment for women with heavily pretreated metastatic breast cancer, for whom there was previously no chemotherapy treatment with proven survival benefit," they add.
Real-World Comparison
Participants in this study had already received 2 to 5 chemotherapy regimens (median, 4; range, 1 to 7), including an anthracycline and a taxane.
They were randomized in a 2:1 ratio to receive either eribulin (1.4 mg/m2 intravenously for 2 to 5 minutes on days 1 to 8 of a 21-day cycle) or TPC. This was defined as any single-agent treatment (chemotherapy, hormonal or biological) or radiotherapy or symptomatic therapy alone. Many physicians chose to use vinorelbine, gemcitabine, or capecitabine, and none chose best supportive care, even though this was an option, said coauthor Christopher Twelves, MD, from the University of Leeds, United Kingdom, when he presented this trial at the ASCO meeting last year.
This represents "a real-life situation," he noted, because there are no guidelines on which chemotherapy to use after third-line therapy.
At the time, the discussant of the paper, Harold Burstein, MD, PhD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, agreed with that description. He makes the same point in an editorial accompanying the study, which he coauthored with his Dana-Farber colleague Nancy Lin, MD.
"Ultimately, the EMBRACE study invited a real-world comparison of best clinical guess versus eribulin," the editorialists write.
The use of TPC is an important strength of this study, say the trialists. Because the results reflect real-life choices made by oncologists and their patients, the benefits of eribulin seen in this trial are "arguably more likely to be generalizable to clinical practice than if the control treatment had been artificially constrained," they write in the paper.
Is Survival Benefit Clinically Meaningful?
The difference between overall survival in the 2 treatment groups was statistically significant; median overall survival was 13.1 months with eribulin and 10.6 months with TPC (hazard ratio, 0.81; P = .041).
This survival benefit is "clinically meaningful," say the trialists, because the median survival benefit of 2.5 months represents an increase of 23% for these women.
This is similar to what has been reported for docetaxel vs mitomycin plus vinblastine (31%), and for capecitabine plus docetaxel vs docetaxel alone (26%).
In addition, they point out that the survival benefit with eribulin was achieved "with a manageable profile of toxic effects." The most common adverse events were asthenia and fatigue (reported by 54% of patients in the eribulin group and 40% in the TPC group) and neutropenia (52% vs 30%). The most common adverse event leading to the discontinuation of eribulin was peripheral neuropathy, occurring in 5% of patients.
However, the editorialists point out that the survival benefit can be measured in weeks, and say that "it is fair to ask whether there is clinical significance."
The outcomes for the TPC group provide "a sobering reminder of the modest results in the nth-line therapy of breast cancer," Dr. Lin and Dr. Burstein note.
Most oncologists participating in a recent survey (Eur J Cancer. 2010;8:77 [abstract 63]) said that they consider prolongation of life by 2 to 6 months to be a "meaningful incremental gain." However, the same survey found that most patients believe that a threshold of 10 months or more is needed to warrant treatment, the editorialists note.
"But surely some survival benefit is better than none at all," they add.
The data from the EMBRACE trial provide "much needed high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," the editorialists write. "And that evidence suggests that the methods to treat advanced breast cancer are growing, the treatment challenge in refractory disease is a little bit less daunting, and the treatment results are a little bit better than they were before."
The EMBRACE study was funded by Eisai. Several of the study authors report receiving consultancy fees, honoraria, and/or grants from Eisai, as well as from several other pharmaceutical companies; full details are given in the paper. Dr. Lin and Dr. Burstein have disclosed no relevant financial relationships.
http://spaineldorado.blogspot.com/2011/03/eribulin-survival-benefit-in-metastatic.html
