Halaven ( Eribulin mesylate ), a non-taxane, microtubule dynamics inhibitor with a novel mechanism of action, belongs to a class of antineoplastic agents, the halichondrins, which are natural products isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequestering tubulin into nonproductive aggregates.
In a phase III clinical study ( EMBRACE ) of Eribulin versus treatment of physician’s choice in 762 patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane, Eribulin showed an extended overall survival of 2.7 months when compared to selected, major existing therapies.
The most common adverse reactions ( events with an incidence rate of at least 25% ) among patients treated with Eribulin were asthenia ( fatigue ), neutropenia, anemia, alopecia, peripheral neuropathy ( numbness and tingling in arms, legs and other parts of the body ), nausea and constipation.
The most common serious side effects reported in patients receiving Eribulin were neutropenia with or without fever ( 4% and 2%, respectively ).
The most common adverse reaction resulting in discontinuation of treatment with Eribulin was peripheral neuropathy ( 5% ).
Furthermore, in a phase II clinical study Eribulin was found to possess excellent anticancer effects and tolerability in patients with advanced or recurrent breast cancer who had previously undergone treatment.
Study 301 was an open-label, randomized, two-parallel-arm, multicenter study designed to evaluate Eribulin versus Capecitabine ( Xeloda ) in 1,102 women with locally advanced or metastatic breast cancer who had up to three prior chemotherapy regimens, and no more than two prior regimens for advanced and/or metastatic disease. The regimens must have included an anthracycline and a taxane, either in the (neo)adjuvant setting, or for locally advanced or metastatic disease.
Patients must have had documented evidence of progression during or after their most recent anticancer therapy. Patients were also randomized according to their human epidermal growth factor receptor 2 ( HER2 ) status ( positive, negative or unknown ) and geographical region ( Eastern Europe, North America, Latin America, Western Europe, South Africa, and Asia ) at a ratio of 1:1 to receive treatment with either Eribulin 1.4 mg/m2/day ( administered intravenously on days 1 and 8, every 21 days ) or Capecitabine 2.5 g/m2/day ( administered orally on days 1 to 14, every 21 days ).
In this study, pre-planned exploratory analyses were conducted based on hormone receptor expression status. The exploratory analyses have shown a benefit of therapy with Eribulin regarding the median overall survival in months in: HER2-negative ( 15.9 vs 13.5 ), estrogen receptor-positive ( 18.2 vs 16.8 ), estrogen receptor-negative ( 14.4 vs 10.5 ), triple negative ( 14.4 vs 9.4 ) cancer. ( Xagena )
Source: Eisai, 2012