Subject: Why HALAVEN(R) (eribulin mesylate) Injection matters Subject Alt 1: See how HALAVEN(R) (eribulin mesylate) Injection may be appropriate for your patients       Essential information about HALAVEN®     Additional information about HALAVEN     Dear [Dr. First Name, Last Name], I'm sorry we missed each other when I stopped by your office. I'm your Eisai Representative and wanted to share some information about HALAVEN that you might find interesting.       Because moments matter, HALAVEN offers an opportunity for a meaningful survival benefit and an established safety profile.1     HALAVEN may be appropriate for your patients who are ready for chemotherapy in third-line mBC and who have received 2 prior chemotherapies for mBC. Their previous treatment should have included an anthracycline and a taxane in the adjuvant or metastatic setting.1     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.     Patients in the HALAVEN arm of the EMBRACE trial:           Results of the updated analysis were consistent with the primary analysis, which was conducted when ~50% of events (deaths) had been observed. HALAVEN demonstrated a median OS of 13.1 months (95% CI: 11.8, 14.3, 274 deaths) vs 10.6 months with the TPC arm (95% CI: 9.3, 12.5, 148 deaths), hazard ratio (HR)=0.81 (95% CI: 0.66, 0.99) (P=0.041)1,2     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 Treatment of Physician's Choice (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. All patients received 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% hormonal therapy.1,2             • 83.1% of patients in the TPC arm had visceral disease3       Read about real-world experience with HALAVEN, after the Selected Safety Information below. mBC=metastatic breast cancer; EMBRACE=Eisai Metastatic Breast Cancer Study Assessing Physician's Choice versus E7389 (Eribulin); CI=confidence interval; OS=overall survival; TPC=Treatment of Physician's Choice.     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.     A growing body of real-world experience         *Patient treatment based on estimates of average patient usage provided by IntrinsiQ® intelliVIEW™.  Total number of vials from November 2010 to December 2017.       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. HALAVEN [package insert]. Woodcliff Lake, NJ: Eisai Inc; 2016. 2. 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. 3. 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. March 2018    HALA-US2061     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.