Eribulin: A New Option in the Treatment of Metastatic Breast Cancer

Breast cancer is the most common cancer among women. In 2010, there were an estimated 207,090 new cases and 39,840 deaths.¹ Despite many improvements in the treatment of breast cancer, about 20% to 30% of women with the disease will progress to metastatic breast cancer (MBC). Although MBC remains incurable, a variety of treatment options are available. The US Food and Drug Administration (FDA) recently approved eribulin (Halaven), providing an exciting new option for women with heavily pretreated MBC.

Eribulin is a synthetic analog of halichondrin B, a nontaxane microtubule dynamics inhibitor originally isolated from a sea sponge. Eribulin inhibits the growth phase of microtubules and sequesters tubulin into nonproductive aggregates, resulting in G2/M cellcycle block, by disrupting mitotic spindles. It exerts its action at a site on the cellular level that is distinct from that targeted by taxanes, vinca alkaloids, and other existing microtubulin inhibitors.

FDA approval was based on data from the international, phase 3 EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus Eribulin) clinical trial, which had a primary end point of overall survival (OS). To be eligible, all the women had to have been treated with 2 to 5 prior chemotherapy regimens and to have experienced disease progression within 6 months of completing their most recent chemotherapy regimen. Of the regimens administered previously in the adjuvant or metastatic setting, at least 1 had to have been anthracycline based and 1 had to have been taxane based to be eligible for enrollment. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and patients with preexisting neuropathy >grade 2 were ineligible.

Investigators randomized 762 patients with MBC at a 2:1 ratio to eribulin (n = 508) or a single-agent therapy selected by their physician prior to randomization (n = 254). Randomization was stratified by geographic region, HER2 status, and prior capecitabine exposure. The physician’s choice of treatment consisted of any single agent, whether a chemotherapy, hormonal, or biologic therapy, or supportive care only. Randomization was stratified by geographic region, HER2 status, and prior capecitabine exposure. Eribulin 1.4 mg/m2 was administered on days 1 and 8 every 21 days, with dose reductions and delays for predetermined toxicities. The control arm therapies consisted of the following agents: vinorelbine (Navelbine; 26%), gemcitabine (Gemzar; 18%), a taxane (16%), capecitabine (18%), an anthracycline (9%), other chemo therapy (10%), and hormonal therapy (3%).

Median OS was significantly prolonged for patients randomized to receive eribulin compared with those who received the physician’s choice of treatment (13.1 vs 10.6 mo, respectively; hazard ratio, 0.809; 95% confidence interval, 0.660-0.991; P = .041).

Eribulin treatment had a manageable safety profile. The most common adverse reactions in the eribulin arm, occurring in >25% of patients, were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation. The most common treatment-related adverse reactions ≥grade 3 experienced by >5% of patients were neutropenia (57%), asthenia/fatigue (10%), and peripheral neuropathy (8%). The most common serious adverse reactions reported in eribulin-treated patients were febrile neutropenia (4%) and neutropenia (2%). The most common toxicity leading to discontinuation of eribulin was peripheral neuropathy (5%).

These results were discussed at the 2010 ASCO Annual Meeting and published in The Lancet in March 2011.² These results are especially noteworthy because this is the first time a single agent has demonstrated survival benefit in this population.

The recommended dosage of eribulin is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on days 1 and 8 of a 21-day cycle. Eribulin may be administered undiluted or diluted in 100 mL of 0.9% sodium chloride injection, USP. The drug should not be administered through an intravenous line that is delivering a dextrose-containing solution.³

Eribulin offers new promise for women with heavily pretreated MBC. The results of the EMBRACE trial demonstrate that cytotoxic therapies directed at a well-defined target remain a viable area of continued study. Given the favorable results of the EMBRACE trial, future studies will examine the use of eribulin in the adjuvant setting and also as frontline therapy in the metastatic setting. It is important for nurses to be aware of the FDA’s approval of eribulin, its mechanism of action, and its safety profile. Nurses are in a pivotal position to advocate for their patients, to provide consistent patient education, and to monitor adverse reactions.

References

1. Breast cancer overview. American Cancer Society. http://www.cancer.org/Cancer/BreastCancer/OverviewGuide/breast-cancer-overview-key-statistics. Up dated September 2010. Accessed April 12, 2011.
2. Cortes J, O’Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomized study. Lancet. 2011;377 (9769):914-923.
3. Halaven [package insert]. Woodcliff Lake, NJ: Eisai, Inc.; 2010.