Drug Extends Overall Survival for Breast Cancer and Liposarcoma

Liposarcoma is one of the most common subtypes of soft tissue sarcomas. Increasing OS is also a challenge in this patient population, with the median survival estimated at 8–13 months for patients with advanced disease starting firstline anthracycline. In addition, in patients for whom surgical resection is not an option, mortality is high.

Halaven^® (eribulin mesylate) injection—a microtubule inhibitor—is indicated for mBC in patients who have previously received at least two chemotherapeutic regimens (including an anthracycline and a taxane in either the adjuvant or metastatic setting) and unresectable or metastatic liposarcoma in those who have received a prior anthracycline-containing regimen.

During a product theater at the 42nd Annual Congress in Denver, CO, Jody Pelusi, PhD, FNP, AOCNP®, advanced oncology certified nurse practitioner at the HonorHealth Research Institute, discussed eribulin mesylate and the role nurses play in managing patients receiving this drug.

The recommended dose of eribulin mesylate is 1.4 mg/m² administered via IV over two to five minutes on days 1 and 8 of a 21-day treatment cycle.

The drug’s U.S. Food and Drug Administration (FDA) approval for mBC was based on the results of the open-label, randomized, multicenter, phase III EMBRACE trial of 762 patients (median age = 55 years; range = 27–85) who were randomized 2:1 based on geographic region, human epidermal growth factor receptor 2/neu status, and prior capecitabine exposure to receive eribulin mesylate 1.4 mg/m₂ (n = 508) or a single agent therapy selected prior to randomization based on physician’s choice (control cohort; n = 254, 97% of patients received chemotherapy, including vinorelbine [26%], gemcitabine [18%], capecitabine [18%], taxane [16%], anthracycline [9%], and other [10%], and the remaining 3% received hormonal therapy).

The study resulted in a statistically significant improvement in median OS (the primary endpoint) in patients receiving eribulin mesylate compared to the control group: 13.2 months (range = 11.8–14.3) versus 10.6 months (range = 9.3–12.5; hazard ratio [HR] = 0.81; 95% CI = 0.66–0.99; p = 0.041). Deaths were reported in 274 eribulin mesylate-treated patients and 148 patients in the control group.

In an updated, unplanned survival analysis, which was conducted when 77% of events had been observed, eribulin mesylate still significantly improved median OS: 13.2 months (range = 12.1–14.4) versus 10.6 months (range = 10.6–12.0). Deaths were reported in 386 eribulin mesylate-treated patients and 203 patients in the control group.

“This is the first and only single agent that significantly extended OS in patients with mBC who had two prior chemotherapeutic regimens,” Pelusi said.

With eribulin mesylate, the objective response rate was 11% (95% CI = 8.6–14.3), and the median duration of response was 4.2 months (95% CI = 3.8–5.0).

The most common any-grade adverse events (AEs) reported in the eribulin mesylate and control cohorts included neutropenia (82% versus 53%), anemia (58% versus 55%), asthenia/fatigue (54% versus 40%), alopecia (45% versus 10%), peripheral neuropathy ([PN], 35% versus 16%), nausea (35% versus 28%), and constipation (25% versus 21%). The most common serious AEs associated with eribulin mesylate were febrile neutropenia (4%) and neutropenia (2%), and the most common AE resulting in treatment discontinuation was PN (5%).

The drug’s FDA approval for unresectable or metastatic liposarcoma was based on results of an open-label, randomized, multicenter, active-controlled, phase III trial of 446 patients (median age = 56 years; range = 24–83) with liposarcoma and leiomyosarcoma who were randomized 1:1 based on histology, number of prior therapies, and geographic region to receive eribulin mesylate 1.4 mg/m² (n = 225) or dacarbazine 850 mg/m², 1,000 mg/m², or 1,200 mg/m² administered every 21 days (n = 221).

The study resulted in a statistically significant improvement in median OS (primary efficacy outcome) in patients specifically with liposarcoma receiving eribulin mesylate (n = 71) compared to dacarbazine (n = 72): 15.6 months (range = 10–18.6) versus 8.4 months (range = 5.2–10.1; HR = 0.51; 95% CI = 0.35–0.75), indicating a 49% reduction in relative risk of death. Deaths were reported in 52 (73%) eribulin mesylate-treated patients and 63 (88%) dacarbazine-treated patients. No evidence of efficacy of eribulin mesylate was found in patients with advanced or metastatic leiomyosarcoma.

“This is the first and only single agent that significantly extended OS in unresectable or metastatic liposarcoma,” Pelusi said.

Progression-free survival was not significantly different between the treatment groups.   

The most common any-grade AEs reported in the eribulin mesylate and dacarbazine cohorts included fatigue, nausea, alopecia, constipation, PN, abdominal pain, and pyrexia. The most common serious AEs associated with eribulin mesylate were neutropenia (4.9%) and pyrexia (4.5%). Eight percent of patients permanently discontinued eribulin mesylate because of AEs, mostly fatigue and thrombocytopenia (0.9% each). Twenty-six percent of patients required at least one dose reduction, mostly because of neutropenia (18%) and PN (4.0%).

Eribulin mesylate has a warning for neutropenia, PN, embryo-fatal toxicity, and QT prolongation. Because of increased PN, “Nurses need to be trained on a one-minute neurologic assessment,” Pelusi said. Nurses should also assess renal and hepatic function prior to starting patients on eribulin mesylate. Establishing Child-Pugh score determines the recommended dose for specific populations with hepatic impairment, which includes an assessment of serum bilirubin, serum albumin, and prothrombin time, as well as two clinical parameters: ascites and grade of encephalopathy. Patients with mild hepatic impairment or with Child-Pugh A scores should receive a dose of 1.1 mg/m², whereas those with moderate hepatic impairment or with Child-Pugh B should receive a dose of 0.7 mg/m².

Complete blood cell counts should be obtained prior to each dose, and if absolute neutrophil counts are < 1000 cells/mm³, platelets are < 75,000 cells/mm³, and grade 3 or 4 nonhematologic toxicities are observed, eribulin mesylate dose on day 1 or day 8 should not be administered. If toxicities resolve or improve to grade ≤ 2 severity by day 15, eribulin mesylate can be administered at a reduced dose and initiate the next cycle no sooner than two weeks later. Once the dose has been reduced, it should not be re-escalated. “Our job as nurse practitioners is to follow patients closely and get them back on track as quickly as possible,” she said.

“We are the intervention,” Pelusi concluded, summarizing the ways that nurses can and should be involved in patient care:

• Assessing and monitoring AEs
• Communicating with patients about the drug’s mechanism of action
• Understanding the safety and efficacy data of eribulin mesylate
• Establishing a baseline of patient function prior to treatment
• Communicating with patients about financial concerns and support programs

Refer to the prescribing information and important safety information for eribulin mesylate for more information.

This program was supported by Eisai, Inc.