Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.
Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.
"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).
A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.
The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.
Patients in the eribulin group received 1.4 mg/m2 eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.
The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.
The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.
About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.
The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.
"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.
In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).
Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.
"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.
The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.
Dr. Lin and Dr. Burstein said they had no conflicts of interest.