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Drs. Valerie Nelson and Mark Agulnik Discuss Improving Survival In Patients With Advanced Liposarcoma

HALAVEN ® (eribulin mesylate) Indication

Liposarcoma

HALAVEN is indicated for the treatment of patients with unresectable or metastatic Advanced Liposarcoma who have received a prior anthracycline-containing regimen.

Please See Important Safety Information below, including Warnings and Precautions for Neutropenia, Peripheral Neuropathy, Embryo-Fetal Toxicity, and QT Prolongation.

Key Study Results:

HALAVEN Increases Overall Survival in Advanced Liposarcoma1
Treatment effects of HALAVEN were limited to patients with Advanced Liposarcoma based on preplanned, exploratory subgroup analyses of OS. There was no evidence of efficacy of HALAVEN in patients with advanced or metastatic leiomyosarcoma in this trial.
Overall Survival Analysis1,2
  Advanced Liposarcoma Stratum All Patients*†
Overall Survival Analysis HALAVEN
(n=71)
Dacarbazine (n=72) HALAVEN
(n=225)
Dacarbazine (n=221)
Median OS, months
(95% CI)
15.6
(10.2-18.6)
8.4
(5.2-10.1)
13.5
(11.1-16.5)
11.3
(9.5-12.6)
Hazard ratio (HR)
(95% CI)
0.51 (0.35-0.75) 0.75 (0.61-0.94)
P value NA 0.011
The FIRST and ONLY single agent that significantly extends overall survival in unresectable or metastatic Advanced Liposarcoma1,2
*All patients = Advanced Liposarcoma and leiomyosarcoma.
Efficacy data from 1 study site enrolling 6 patients were excluded.
CI = confidence interval; NA = not applicable.

 

The efficacy and safety of HALAVEN were evaluated in an open-label, randomized (1:1), multicenter, active-controlled trial. Eligible patients were required to have unresectable, locally advanced, or metastatic Advanced Liposarcoma or leiomyosarcoma, at least 2 prior systemic chemotherapies (1 of which must have included an anthracycline), and disease progression within 6 months of the most recent chemotherapy regimen. Patients were randomized to HALAVEN 1.4 mg/m2 administered intravenously on days 1 and 8 of a 21-day cycle or to dacarbazine at a dose of 850 mg/m2, 1,000 mg/m2, or 1,200 mg/m2 administered intravenously every 21 days (dacarbazine dose was selected by the investigator prior to randomization). Treatment continued until disease progression or unacceptable toxicity. Randomization was stratified by histology (Advanced Liposarcoma or leiomyosarcoma), number of prior therapies (2 vs >2), and geographic region. The most common (>40%) prior systemic chemotherapies were doxorubicin (90%), ifosfamide (62%), gemcitabine (59%), trabectedin (50%), and docetaxel (48%).1

- Halaven is the first and only single agent to show a significant overall survival benefit in a phase 3 study of patients with advanced Liposarcoma

- Treatment with Halaven in patients with Advanced Liposarcoma resulted in a 7-months improvement in median overall survival compared to the dacarbazine arm (15.6 vs. 8.4)

- Patients in the Halaven arm with Advanced Liposarcoma had an 86% increase in median survival time vs. control group

- Patients who received dose reductions, dose delays, or discontinued therapy were included in the overall survival analysis of the clinical trial

Important Safety Information

Warnings and Precautions

Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC and Advanced Liposarcoma or leiomyosarcoma. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Febrile neutropenia occurred in 0.9% of patients with Advanced Liposarcoma or leiomyosarcoma, and fatal neutropenic sepsis occurred in 0.9% of patients. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels. Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days.

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC. Grade 3 peripheral neuropathy occurred in 3.1% of patients with Advanced Liposarcoma and leiomyosarcoma receiving HALAVEN and neuropathy lasting more than 60 days occurred in 58% (38/65) of patients who had neuropathy at the last treatment visit. Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less.

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid in patients with congenital long QT syndrome.

Adverse Reactions

In patients with Advanced Liposarcoma and leiomyosarcoma receiving HALAVEN, the most common adverse reactions (≥25%) reported in patients receiving HALAVEN were fatigue (62%), nausea (41%), alopecia (35%), constipation (32%), peripheral neuropathy (29%), abdominal pain (29%), and pyrexia (28%). The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia (32%), hypokalemia (5.4%), and hypocalcemia (5%). Neutropenia (4.9%) and pyrexia (4.5%) were the most common serious adverse reactions. The most common adverse reactions resulting in discontinuation were fatigue and thrombocytopenia (0.9% each).

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

Please see the Halaven full prescribing information below.

HCPs participating in this video were compensated for their time.

References

1. HALAVEN [package insert]. Woodcliff Lake, NJ: Eisai Inc.; October 2016.

2. Schöffski P, Chawla S, Maki RG, et al. Eribulin versus dacarbazine in previously treated patients with advanced Advanced Liposarcoma or leiomyosarcoma: a randomized, open-label, multicentre, phase 3 trial. Lancet. 2016;387 (10028): 1629-1637.

Additional important safety Information can be found below and information about Halaven can be found at www.halaven.com