Subject:
Eribulin Mesylate (Halaven)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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HalavenTM (eribulin mesylate) injection is approved by the FDA for the third-line treatment of metastatic breast cancer in patients who have previously been treated with at least two chemotherapy regimens including an anthracycline and taxane. Halaven is a nontaxane microtubule dynamics inhibitor that is manufactured from a marine sponge. The recommended dose of Halaven™ is 1.4mg/m2 administered intravenously over two to five minutes on days one and eight of a 21-day cycle.
A phase III open-label, multicenter, randomized study was conducted looking at the efficacy of eribulin. Patients were women with locally recurrent or metastatic breast cancer that had received 2-5 prior chemotherapy (2 or more for advanced disease) which included an anthracycline and a taxane, unless contraindicated. Patients were randomized 2:1 to eribulin 1.4mg/m2 2-5 minutes IV bolus on days 1 and 8 of a 21-day cycle or treatment of physician’s choice (TPC) (cytotoxic, hormonal, biologic) or supportive care only. There were 508 patients in the eribulin mesylate arm and 254 in the TPC arm. The primary endpoint looked at the overall survival and the secondary endpoints looked at the objective response rate, progression-free survival by independent review, and duration of response. The median overall survival was 13.1 months for eribulin versus 10.7 months for TPC (p=0.04; HR 0.85; 95% CI 0.70, 1.03). The objective response rate was 12% (0.4% complete response, 11.5% partial response) for eribulin and 5% (0 complete response; 5% partial response) for TPC (p=0.005). The median duration of response was 4.1 months for eribulin with 56 responders versus 6.7 months for TPC with 11 responders. The most common treatment-related adverse events for eribulin were asthenia/fatigue (7.6%), neutropenia (44%), and peripheral neuropathy (8.4%). Treatment-related serious adverse events were slightly higher in the eribulin arm at 12% versus 7% in the TPC arm.
Halaven™ received FDA-approval for liposarcoma on January 28th, 2016, having priority review status and also receiving orphan drug designation for this indication. The efficacy of Halaven™ was evaluated in Study 2, an open-label, randomized (1:1), multicenter, active-controlled trial. Eligible patients were required to have unresectable, locally advanced, or metastatic liposarcoma or leiomyosarcoma, at least two prior systemic chemotherapies (one including anthracycline), and disease progression within 6 months of the most recent regimen. Patients were randomized to Halaven™ 1.4 mg/m2 administered IV on days 1 and 8 of a 21 day cycle regimen, or dacarbazine 850 mg/m2, 1000 mg/m2, or 1200 mg/m2 IV every 21 days. The primary efficacy outcome was overall survival (OS), and other outcomes measured include progression-free survival (PFS) and confirmed objective response rate (ORR).
Of the 143 patients with liposarcoma 52 (73%) with Halaven™ versus 63 (88%) on dacarbazine died, resulting in a Hazard Ratio of 0.51 (95% CI, 0.35, 0.75). Patients on Halaven™ also demonstrated a benefit with regards to progression-free survival [HR 0.52 (95% CI, 0.35, 0.78)]. The results were not significant for PFS in the overall population.
The most common adverse reactions (≥25%) reported in patients receiving HALAVEN were fatigue, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia. The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia, hypokalemia, and hypocalcemia. The most common serious adverse reactions reported in patients receiving HALAVEN were neutropenia (4.9 %) and pyrexia (4.5%). Permanent discontinuation of HALAVEN for adverse reactions occurred in 8% of patients. The most common adverse reactions resulting in discontinuation of HALAVEN were fatigue and thrombocytopenia (0.9% each). Twenty-six percent of patients required at least one dose reduction. The most frequent adverse reactions that led to dose reduction were neutropenia (18%) and peripheral neuropathy (4.0%).
Policy:
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
The requirements of the Horizon BCBSNJ Eribulin Mesylate (Halaven) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
1. The prescriber is a specialist in the area of the patient's diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient's diagnosis.
2. Eribulin mesylate (Halaven) is considered medically necessary for the following FDA-approved indications:
- Locally recurrent or metastatic breast cancer when all of the following criteria are met:
- Member is at 18 years of age or older; AND
- Member received at least two prior chemotherapies. (Prior therapy should include an anthracyclines, and a taxanes in either the adjuvant or metastatic setting) AND
- Member does not have severe hepatic impairment (Child Pugh C)
- Unresectable or metastatic liposarcoma when all of the following criteria are met:
- Member is at 18 years of age or older; AND
- Member has received a prior chemotherapies including an anthracycline-containing regimen AND
- Member does not have severe hepatic impairment (Child Pugh C)
[INFORMATIONAL NOTE: As per the FDA package insert, patients with severe hepatic impairment were not included in the pivotal clinical studies for either indication]
3. When eribulin mesylate (Halaven) is considered medically necessary, initial therapy authorized for a period of 6 months based on the FDA-recommendations:
- 1.4 mg/m2 intravenously over 2-5 minutes on days 1 and 8 of 21-day cycle
- Member must have absolute neutrophil count (ANC) of at least 1,000/mm3, platelet count of at least 75,000/mm3 and no signs of grade 3 or 4 non-hematological toxicities on Day 1 or Day 8 of administration.
[INFORMATIONAL NOTE:
As per the FDA approved package insert, dosage adjustment
- In mild hepatic impairment (Child-Pugh A) or moderate renal impairment (Creatinine Clearance of 30-50ml/min): 1.1 mg/m2 Intravenously over 2-5 minutes on days 1 and 8
- In moderate hepatic impairment (Child-Pugh B): 0.7 mg/m2 Intravenously over 2-5 minutes on days 1 and 8
- If member’s ANC< 500/mm3 for >7 days, ANC< 1,000/mm3 with fever or infection, platelet <25,000/mm3, platelet <50,000/mm3 requiring transfusion, have non-hematologic Grade 3 or 4 toxicities eribulin’s or have an omission or delay of Day 8 dose in previous cycle for toxicity dose should be reduced to 1.1 mg/m2]
4. Continued therapy will be authorized every 6 months when
- Member continues to meet initial review criteria; AND
- Member had disease response defined as lack of disease progression, improvement in tumor size and/or improvement in patient symptoms; AND
- Absence of unacceptable toxicity from the drug (e.g.: neutropenia, peripheral neuropathy, QT prolongation) AND
- Member does not have severe hepatic impairment (Child Pugh C)
5. Eribulin mesylate (Halaven) is considered medically necessary for the off-label indications that are 2A or better recommendations on National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - Eribulin mesylate. Available at: https://www.nccn.org/professionals/drug_compendium/content/.
6. All other uses of eribulin mesylate (Halaven) are considered investigational.
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Eribulin Mesylate (Halaven)
Halaven (Eribulin Mesylate)
References:
1. Twelves D, Loesch JL, BLUM L, et al. A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician’s choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane. 2010 ASCO Annual Meeting. Oral Abstract Session, Breast Cancer – Metastatic, Abstract No: CRA1004.
2. National Cancer Institute. General Information about Breast Cancer. 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/breast/healthprofessional#Section_10
3. National Cancer Institute. Treatment Options by Stage. 2010. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/breast/Patient/page6#Section_260
4. The “EMBRACE” Trial: Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389. A Phase III Open-Label, Randomized, Parallel, Two-arm, Multi-center Study of E7389 Versus "Treatment of Physician's Choice" in Patients With Locally Recurrent, Metastatic Breast Cancer, Previously Treated With At Least Two and a Maximum of Five Prior Chemotherapy Regimens, Including an Anthracycline and a Taxane. Study NCT00388726. Available at: http://www.clinicaltrial.gov.
5. Halaven (eribulin mesylate). [Prescribing Information] Woodcliff Lake NJ: Eisai. Dec 2017.
6. Eribulin mesylate. National Comprehensive Cancer Network: Drugs and Biologics Compendium. [Available at http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=367 (accessed 4/27/2020)]
7. ClinicalTrials.gov. Halaven. Available at https://clinicaltrials.gov/ct2/results?cond=&term=halaven&cntry=&state=&city=&dist=. Accessed 04/27/2020
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
J9179
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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