Eribulin Improves Survival in Advanced Sarcoma

News | June 03, 2015 | Sarcoma, ASCO 2015

By Mark L. Fuerst
Treating advanced sarcoma with the chemotherapy agent eribulin improves
overall survival compared with treatment with standard therapy with
dacarbazine, according to the results of a randomized, open-label, multicenter
phase III trial (abstract LBA10502) presented at the American Society of Clinical
Oncology (ASCO) Annual Meeting, held May 29 to June 2, in Chicago.

This is the first phase III trial investigating patients with soft-tissue sarcoma to
demonstrate an overall survival benefit compared with an active agent, said
lead author Patrick Schffski, MD, MPH, head of the department of general
medical oncology at University Hospitals Leuven in Leuven, Belgium.

Soft-tissue sarcoma is a heterogeneous family of rare diseases, and liposarcoma

and leiomyosarcoma are among the more common subtypes. Patients with
advanced, metastatic soft-tissue sarcoma have poor outcomes with limited
treatment options.

Eribulin, a microtubule dynamics inhibitor, is a synthetic analog of halichondrin

B, originating from a marine sponge product. It is primarily a cytotoxic compound
that, based on preclinical findings, kills cancer cells via antimitotic effects,
Schffski said.

In preclinical models, eribulin also affects tumor cells via vascular remodeling,
reversal of epithelial-mesenchymal transition, suppression of migration, and
invasion. The drug is approved in 59 countries as monotherapy in multiple lines
for patients with advanced/metastatic breast cancer.

The efficacy of available drugs for initial therapy of sarcomas is very

unsatisfactory, and patients whose disease progresses despite two or more lines
of treatment have a very poor prognosis, Schffski said. Typically, survival is 1
year or less for the estimated 12,000 people who will be diagnosed this year in
the United States with soft-tissue sarcoma.

In the study, 452 sarcoma patients, about three-quarters of them under age 65
years, were randomly assigned to receive either eribulin 1.4 mg/m2
intravenously on days 1 and 8 (228 patients) or dacarbazine 8501,200 mg/m2
intravenously on day 1 (224 patients) every 21 days until disease progression. All
patients had received at least two standard systemic treatment regimens,
including an anthracycline.

The trials primary endpoint, overall survival, was met. Patients treated with
eribulin experienced a statistically significant improvement in median overall
survival as compared with dacarbazine (13.5 months vs 11.5 months; hazard
ratio = 0.768; P = .0169), Schffski said. Median progression-free survival was
2.6 months in both arms.

Adverse events were in line with the known safety profiles, he said. The most
common frequent treatment-related adverse events in the eribulin arm were
neutropenia, fatigue, nausea, alopecia, and constipation; 8% of patients stopped
treatment due to side effects.

Low platelet counts were more common in the dacarbazine group compared with
the eribulin group. Grade 3 and 4 treatment-related side effects occurred more
frequently with eribulin than dacarbazine.

For a disease where such few treatment options exist, a 2-month improvement
in survival is significant. The more treatments our patients have access to, the
better their chances of improving life expectancy, Schffski said.

Gary K. Schwartz, MD, professor of medicine at Columbia University Medical

Center, commented: This is a giant step forward in sarcoma. There has never
been a positive study for survival in sarcoma. The side effects are manageable,
he added, and must be balanced against the drugs benefits

- See more at: http://www.cancernetwork.com/asco-2015/eribulin-improvessurvival-advanced-sarcoma#sthash.a4B7YeLB.dpuf