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Halaven, 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. Halaven was first approved as a treatment for breast cancer in the United States in November 2010, and is approved in more than 50 countries worldwide, including European Union member states, Japan, Singapore and Switzerland. Furthermore, with the aim of maximizing value of the drug, ºÚÁÏÍø is currently moving ahead with developments investigating the potential of Halaven as a therapy in the treatment of breast cancer with fewer prior treatments as well as soft-tissue sarcoma and non-small cell lung cancer.

The pooled analysis included data from EMBRACE (ºÚÁÏÍø Metastatic Breast Cancer Study Assessing Treatment of Physician's Choice (TPC) Versus Eribulin) and involved women who received 2-5 lines of chemotherapy for advanced disease. In this third line setting, women were randomized 2:1 to receive eribulin (1.4 mg/m² iv on days 1 and 8 every 21 days) or TPC. The second study in the pooled analysis (study 301) included women who had received 0-2 prior chemotherapies for advanced disease who were randomized 1:1 to receive either eribulin (dose schedule as per EMBRACE) or capecitabine (1.25 g/m² orally twice daily on days 1-14 every 21 days). Overall survival was analyzed in the overall intent-to-treat (ITT) population and in subgroups based on HER2 and hormone-receptor status.

In the Phase Ⅲ clinical study (Study 305, EMBRACE) of Halaven versus treatment of physician's choice (TPC) in 762 patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane, Halaven indicated extended overall survival (OS) of 2.5 months (OS of 13.1 months versus 10.6 months, respectively; Hazard Ratio (HR) 0.81; p=0.041) when compared to selected, major existing therapies. An updated analysis of OS (not protocol-specified) in the EMBRACE study was also performed at the request of European and U.S. regulatory authorities. These results demonstrated an increase of 2.7 months in OS for Halaven compared with TPC (OS of 13.2 months versus 10.5 months, respectively; HR 0.81; p=0.014). The most common adverse reactions (events with an incidence rate of at least 25%) among patients treated with Halaven were asthenia (fatigue), neutropenia, alopecia (hair loss), peripheral neuropathy (numbness and tingling in arms, legs and/or other parts of the body), nausea and constipation. The most common serious side effects reported in patients receiving Halaven were neutropenia. The most common adverse reaction resulting in discontinuation of treatment with Halaven was peripheral neuropathy (5%).

Study 301 was an open-label, randomized, two-parallel-arm, multicenter study designed to evaluate Halaven versus capecitabine in 1,102 women with locally advanced or metastatic breast cancer who had up to three prior chemotherapy regimens in the (neo)adjuvant setting, and no more than two prior regimens for locally advanced and/or metastatic disease. The regimens must have included an anthracycline and a taxane. Although eribulin did not achieve a statistically significant result when compared to capecitabine in terms of overall survival (OS) and progression-free survival (PFS), the co-primary endpoints of the study, eribulin did demonstrate a trend favoring improved OS (eribulin median OS: 15.9 months, capecitabine median OS: 14.5 months; HR 0.879; 95% CI: 0.770-1.003; p=0.056). Additionally, a later PFS assessment carried out by an independent evaluation body concluded that there was no significant difference between the two drugs (eribulin median PFS: 4.1 months, capecitabine median PFS: 4.2 months, HR 1.079; 95% CI: 0.932-1.250; p=0.305). In regard to safety, adverse events (AEs) were consistent with the known side-effect profiles of both drugs. The most common AEs (events with an incidence rate of at least 20%) for Halaven and capecitabine were, respectively, neutropenia (54.2% vs. 15.9%), hand-foot syndrome (0.2% vs. 45.1%), alopecia (34.6% vs. 4.0%), leukopenia (31.4% vs. 10.4%), diarrhea (14.3% vs. 28.8%), and nausea (22.2% vs. 24.4%).

HER2 is a protein that is found on the surface of cells. In HER2-positive breast cancer there is more (over expression) of this protein found on the surface of tumor cells compared with normal breast cells. This protein can be targeted with HER2 targeted therapies in people who overexpress HER2, but not in people with normal levels of HER2 protein (HER2-negative) breast cancer. Breast cancers are routinely tested for the presence of HER2 to decide the most appropriate treatment. HER2 negative breast cancer is a subtype that affects an estimated 85% of women with breast cancer. Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for estrogen receptor, progesterone receptor and HER2.