PRIOR AUTHORIZATION CRITERIA MN-026 HALAVEN (Eribulin)

PRIOR AUTHORIZATION CRITERIA MN-026 HALAVEN (eribulin)

Medication Class: ANTINEOPLASTIC - non-taxane microtubule dynamics inhibitor Review Date: 02/01/2015, 12/26/2017, 11/29/2018, 10/7/2019, 10/29/2019, 11/19/2019, 11/12/2020 Available Through: □ Medical Benefit □ Pharmacy Benefit Page | 1 Available Dosage Forms: NDC 62856-389-01 Eribulin mesylate injection, 1 mg/2 mL, in a single-use vial. One vial per carton. Usual Dose: See Dosage below Duration of Therapy: 6 months Brand Name: HALAVEN Generic Name: eribulin Mesylate INDICATION: Requires Diagnosis AND Recurrent or Metastatic Initial Therapy Breast Cancer • There is now relapsed or refractory disease; AND EITHER: o For members of Plans subject to Texas Mandate HB 1584: the member has stage 4 advanced metastatic disease; OR o Used as subsequent therapy for patients who have previously received therapy with an anthracycline and a taxane • Treatment as a single agent for recurrent or metastatic human epidermal growth factor receptor (HER2)-negative disease: o with symptomatic visceral disease or visceral crisis OR o that is hormone receptor-negative OR o hormone receptor-positive AND EITHER: . For members of Plans subject to Texas Mandate HB 1584: the member has stage 4 advanced metastatic disease; OR . Endocrine therapy refractory OR • Therapy in combination with trastuzumab for HER2-positive recurrent or metastatic trastuzumab-exposed disease: o with symptomatic visceral disease or visceral crisis OR o that is hormone receptor-negative OR o hormone receptor-positive AND EITHER: . For members of Plans subject to Texas Mandate HB 1584: the member has stage 4 advanced metastatic disease; OR . Endocrine therapy refractory

Continuation Therapy • Clinical documentation showing lack of disease progression, such as clinical notes, laboratory testing, imaging reports (DOCUMENTATION REQUIRED)

NOTE: Intolerance or previous trial/failure of traditional therapy must be must be supplied for review through physician chart note, or through patient’s pharmacy history.

Soft Tissue Sarcoma Initial Therapy • Use as single agent palliative therapy for the following soft tissue Page | 2 sarcomas: o angiosarcoma; OR o unresectable or metastatic liposarcoma AND EITHER: . For members of Plans subject to Texas Mandate HB 1584: the member has stage 4 advanced metastatic disease; OR . Received prior anthracycline-containing regimen; OR o unresectable or progressive retroperitoneal/intraabdominal soft tissue sarcoma; OR o pleomorphic rhabdomyosarcoma; OR o synchronous stage IV or recurrent soft tissue sarcoma of the extremity/superficial trunk, head/neck with disseminated metastases • Use as single agent therapy for uterine sarcoma

Continuation Therapy • Clinical documentation showing lack of disease progression, such as clinical notes, laboratory testing, imaging reports (DOCUMENTATION REQUIRED) • Clinical documentation showing absence of unacceptable toxicities (DOCUMENTATION REQUIRED), including: severe QT-prolongation, severe neutropenia, and peripheral neuropathy

NOT COVERED FirstCare considers eribulin mesylate experimental and investigational for all other indications including the following (not an all-inclusive list) because its effectiveness for these indications has not been established:

• Brain metastases (e.g., leptomeningeal carcinomatosis) from other solid tumors, and from breast cancer in persons who do not meet above listed criteria • Fallopian tube cancer • Head and neck cancer • Non-small-cell • lung cancer • Ovarian cancer • Pancreatic cancer • Peritoneal cancer • Prostate cancer NOTE: Intolerance or previous trial/failure of traditional therapy must be must be supplied for review through physician chart note, or through patient’s pharmacy history.

DOSAGE Recommended Dose The recommended dose of HALAVEN is 1.4 mg/m² administered intravenously over 2 to 5 minutes on Days 1 Page | 3 and 8 of a 21-day cycle.

The recommended dose of HALAVEN in patients with mild hepatic impairment (Child-Pugh A) is 1.1 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

The recommended dose of HALAVEN in patients with moderate hepatic impairment (Child-Pugh B) is 0.7 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

The recommended dose of HALAVEN in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min) is 1.1 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

Dose Modification Assess for peripheral neuropathy and obtain complete blood cell counts prior to each dose.

Recommended Dose Delays

• Do not administer HALAVEN on Day 1 or Day 8 for any of the following: • ANC < 1,000/mm³ • Platelets < 75,000/mm³ • Grade 3 or 4 non-hematological toxicities. • The Day 8 dose may be delayed for a maximum of 1 week. • If toxicities do not resolve or improve to ≤ Grade 2 severity by Day 15, omit the dose. • If toxicities resolve or improve to ≤ Grade 2 severity by Day 15, administer HALAVEN at a reduced dose and initiate the next cycle no sooner than 2 weeks later.

Recommended Dose Reductions

• If a dose has been delayed for toxicity and toxicities have recovered to Grade 2 severity or less, resume HALAVEN at a reduced dose as set out in Table 1. • Do not re-escalate HALAVEN dose after it has been reduced.

Table 1 : Recommended Dose Reductions

NOTE: Intolerance or previous trial/failure of traditional therapy must be must be supplied for review through physician chart note, or through patient’s pharmacy history.

RECOMMENDED EVENT DESCRIPTION HALAVEN DOSE

Permanently reduce the 1.4 mg/m² HALAVEN dose for any of the Page | 4 following:

ANC < 500/mm³ for > 7 days

ANC < 1,000 /mm³ with fever or infection

Platelets < 25,000/mm³ 1.1 mg/m²

Platelets < 50,000/mm³ requiring transfusion

Non-hematologic Grade 3 or 4 toxicities

Omission or delay of Day 8 HALAVEN dose in previous cycle for toxicity

Occurrence of any event requiring permanent 0.7 mg/m² dose reduction while receiving 1.1 mg/m²

Occurrence of any event requiring permanent Discontinue dose reduction while receiving 0.7 mg/m² HALAVEN

ANC = absolute neutrophil count. Toxicities graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Instructions For Preparation And Administration Aseptically withdraw the required amount of HALAVEN from the single-use vial and administer undiluted or diluted in 100 mL of 0.9% Sodium Chloride Injection, USP.

Do not dilute in or administer through an intravenous line containing solutions with dextrose. Do not administer in the same intravenous line concurrent with the other medicinal products.

NOTE: Intolerance or previous trial/failure of traditional therapy must be must be supplied for review through physician chart note, or through patient’s pharmacy history.

Discard unused portions of the vial. Page | 5

CPT-Codes/HCPCS Codes/ICD-10 Codes CPT/HCPCS codes covered if selection criteria are met:

J9179 Injection, eribulin mesylate, 0.1

Other CPT/HCPCS codes related to the CPB:

96409 Chemotherapy administration; intravenous, push technique, single or initial substance/drug

J9000 Injection, doxorubicin HCl, 10 mg

J9150 Injection, daunorubicin, 10 mg

J9178 Injection, epirubicin HCl, 2 mg

J9200 Injection, floxuridine, 500 mg

J9355 Injection, trastuzumab, 10 mg

J9357 Injection, valrubicin, intravesical, 200 mg

ICD-10 codes covered if selection criteria are met:

C50.011 - C50.929 Malignant neoplasm of breast [for individuals with recurrent or metastatic breast cancer]

C48.0 - C48.8 Malignant neoplasm of retroperitoneum and peritoneum

C49.0 - C49.9 Malignant neoplasm of other connective tissue and soft tissue

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):

C00.0 – C47.9, Malignant neoplasm [except recurrent or metastatic breast cancer, angiosarcoma, C51.0 – D09.9 pleomorphic rhabdomyosarcoma, unresectable of progressive retroperitoneal/intraabdominal soft tissue sarcoma, and synchronous stage IV or recurrent soft tissue sarcoma of the extremity/superficial trunk with disseminated metastases]

REFERENCES: The above policy is based on the following references:

NOTE: Intolerance or previous trial/failure of traditional therapy must be must be supplied for review through physician chart note, or through patient’s pharmacy history.

*Medical PA requests are reviewed by FirstCare for in-office administration only. For outpatient home administration, PA requests must go through pharmacy benefit, and submitted via PBM: http://www.firstcare.com/FirstCare/media/First- Care/PDFs/RX_FirstCare_Prior-Authorization-List.pdf PRIOR AUTHORIZATION CRITERIA MN-026 HALAVEN (eribulin) 1. Perry CM. Eribulin. Drugs. 2011;71(10):13211331. 2. National Horizon Scanning Centre (NHSC). Eribulin for locally advanced or metastatic breast cancer third line; monotherapy. Horizon Scanning Technology Briefing. Birmingham, UK: National Horizon Scanning Centre (NHSC); 2009. 3. Aogi K, Iwata H, Masuda N, et al. A phase II study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer. Ann Oncol. 2012;23(6):14411448. Page | 6 4. 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 openlabel randomised study. Lancet. 2011;377(9769):914923. 5. U.S. Food and Drug Administration (FDA). FDA approves new treatment option for latestage breast cancer. Press Release. Silver spring, MD: FDA; November 15, 2010. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm233863.htm. Accessed July 23, 2012. 6. National Comprehensive Cancer Network (NCCN). Eribulin. NCCN Drugs and Biologics Compendium. Fort Washington, PA: NCCN; 2012. 7. Schoffski P, RayCoquard IL, Cioffi A, et al; European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG). Activity of eribulin mesylate in patients with softtissue sarcoma: A phase 2 study in four independent histological subtypes. Lancet Oncol. 2011;12(11):10451052. 8. Mathis S, Alberti C, Czeczot J, et al. Eribulin (Halaven) as thirdor lateline monotherapy for advanced/metastatic breast cancer. Decision Support Document. Horizon Scanning in Oncology No. 18. Vienna, Austria: Ludwig Boltzmann Institut fuer Health Technology Assessment (LBIHTA); 2011. 9. Hensley ML, Kravetz S, Jia X, et al. Eribulin mesylate (halichondrin B analog E7389) in platinumresistant and platinumsensitive ovarian cancer: A 2cohort, phase 2 study. Cancer. 2012;118(9):24032410. 10. de Bono JS, Molife LR, Sonpavde G, et al. Phase II study of eribulin mesylate (E7389) in patients with metastatic castrationresistant prostate cancer stratified by prior taxane therapy. Ann Oncol. 2012;23(5):12411249. 11. Scarpace SL. Eribulin mesylate (e7389): Review of efficacy and tolerability in breast, pancreatic, head and neck, and nonsmall cell lung cancer. Clin Ther.2012;34(7):14671473. 12. Pean E, Klaar S, Gil Berglund E, et al. The European Medicines Agency review of eribulin (Halaven) for the treatment of patients with locally advanced or metastatic breast cancer: Summary of the scientific assessment of the committee for medicinal products for human use (CHMP). Clin Cancer Res. 2012;18(17):44914497. 13. National Institute for Health and Clinical Excellence (NICE). Eribulin for the treatment of locally advanced or metastatic breast cancer. Technology Appraisal Guidance 250. London, UK: NICE; April 2012. 14. Eisai Inc. Halaven (eribulin mesylate) Injection. Prescibing Information. Reference ID: 2863825. Woodcliff Lake, NJ; Eisai; revised November 2010. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201532lbl.pdf. Accessed July 23, 2012. 15. Gitlitz BJ, TsaoWei DD, Groshen S, et al. A phase II study of halichondrin B analog eribulin mesylate (E7389) in patients with advanced nonsmall cell lung cancer previously treated with a taxane: A California cancer consortium trial. J Thorac Oncol. 2012;7(3):574578. 16. Preston JN, Trivedi MV. Eribulin: A novel cytotoxic chemotherapy agent. Ann Pharmacother. 2012;46(6):802811.

NOTE: Intolerance or previous trial/failure of traditional therapy must be must be supplied for review through physician chart note, or through patient’s pharmacy history.