Efficacy and safety of HALAVEN®     Additional information about HALAVEN View this email in browser     Dear Dr. %%First_Name%% %%Last_Name%%, Take a closer look at HALAVEN as a treatment option for your patients. We hope that you find the following information on its effectiveness and safety to be helpful.       HALAVEN offers a significant overall survival (OS) benefit in patients with third-line metastatic breast cancer following 2 prior chemotherapies for metastatic breast cancer1-4       A MEANINGFUL SURVIVAL BENEFIT     The first and only single agent that significantly extended life in third-line mBC1-3       Indication       Metastatic Breast Cancer HALAVEN (eribulin mesylate) Injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.       UPDATED OS ANALYSIS (UNPLANNED): MEDIAN OS, MONTHS (95% CI)1,4,a       CI=confidence interval. aConducted in the intent-to-treat (ITT) population.     Results of the updated analysis were consistent with the primary analysis, which was conducted when ~50% of events (deaths) had been observed. HALAVEN demonstrated median OS of 13.1 months (95% CI: 11.8, 14.3) vs 10.6 months with the Treatment of Physician's Choice (TPC) arm (95% CI: 9.3, 12.5), hazard ratio (HR)=0.81 (95% CI: 0.66, 0.99) (P=0.041).1,4     Results from an updated, unplanned survival analysis of the Phase III, randomized, open-label, multicenter, multinational Eisai Metastatic Breast Cancer Study Assessing Physician's Choice versus E7389 (Eribulin) (EMBRACE) trial of HALAVEN versus TPC in patients with mBC (N=762), conducted when 77% of events (deaths) had been observed. The primary endpoint was OS. Patients were randomized (2:1) to receive either HALAVEN 1.4 mg/m2 intravenously for 2 to 5 minutes on Days 1 and 8 of a 21-day cycle, or any single-agent therapy, selected prior to randomization. At baseline, all patients had received ≥2 prior chemotherapeutic regimens for metastatic disease and demonstrated disease progression within 6 months of their last chemotherapeutic regimen. Patients were required to receive prior anthracycline- and taxane-based chemotherapy. Therapies in the TPC arm consisted of 97% chemotherapy (26% vinorelbine, 18% gemcitabine, 18% capecitabine, 16% taxanes [included paclitaxel, docetaxel, nab-paclitaxel, and ixabepilone], 9% anthracyclines, 10% other chemotherapy) and 3% hormone therapy.1,4     Read about the post hoc exploratory analysis of OS with HALAVEN, after the Selected Safety Information below.       Selected Safety Information       Warnings and Precautions       Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 x ULN and bilirubin >1.5 x 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.       Please see additional Selected Safety Information below.     Exploratory analysis: OS by patient subgroups5       Limitations1,5       • Exploratory subgroup analyses were not prespecified, adjusted for multiplicity, or powered to show statistical significance • The wide and overlapping CIs and small numbers of subjects in certain subgroups mean that no conclusions can be drawn     Selected Safety Information     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. 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 mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions. The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%).       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. For more information, please visit www.halaven.com. Please see the HALAVEN full Prescribing Information.     References: 1. Cortes J, O'Shaughnessy J, Loesch D, et al. EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377(9769):914-923. 2. Saad ED, Katz A, Buyse M. Overall survival and post-progression survival in advanced breast cancer: a review of recent randomized clinical trials. J Clin Oncol. 2010;28(11):1958-1962. 3. Sparano JA, Vrdoljak E, Rixe O, et al. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010;28(20):3256-3263. 4. HALAVEN [package insert]. Woodcliff Lake, NJ: Eisai Inc; 2016. 5. Data on file, Eisai Inc.         HALAVEN® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd. © 2018 Eisai Inc. All rights reserved. July 2018  HALA-US2219       Eisai Inc. | 100‍ Ti‍ce Bl‍vd. | Wood‍cliff La‍ke, N‍J 076‍77 Please DO NOT REPLY TO THIS E-MAIL. Eisai will not receive this message if you reply. To unsubscribe from future HALAVEN emails, click here.