Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Eribulin Mesylate (Halaven®)
Policy #:MA08.056c

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

MEDICALLY NECESSARY

Eribulin mesylate (Halaven®) is considered medically necessary and, therefore, covered for any of the following indications:
  • Breast cancer for any of the following:
    • Treatment for individuals with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant (after breast cancer surgery) or metastatic setting.
      • Individuals who are ineligible for an anthracycline agent due to cardiac dysfunction are excluded from this stipulation.
    • Single-agent treatment for individuals with recurrent or metastatic human epidermal growth factor receptor 2-negative (HER-2) invasive breast cancer that is any of the following:
      • With symptomatic visceral disease or visceral crisis
      • That is either hormone receptor--negative or hormone receptor--positive and endocrine therapy refractory
    • Therapy in combination with trastuzumab (Herceptin®) for HER 2-positive recurrent or metastatic trastuzumab (Herceptin®)-exposed invasive breast cancer that is either of the following:
      • With symptomatic visceral disease or visceral crisis
      • That is either hormone receptor-negative or hormone receptor-positive and endocrine therapy refractory
  • Soft tissue sarcoma for any of the following:
    • Treatment of individuals with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen
    • Single-agent palliative therapy for individuals with angiosarcoma
    • Single-agent palliative therapy for individuals with pleomorphic rhabdomyosarcoma
    • Single-agent palliative therapy for individuals with liposarcoma
    • Single-agent palliative chemotherapy for individuals with synchronous stage IV or recurrent disease of the extremity/superficial trunk, head/neck, with disseminated metastases
    • Single-agent palliative chemotherapy for individuals with unresectable or progressive retroperitoneal/intra-abdominal disease

EXPERIMENTAL/INVESTIGATIONAL

All other uses of eribulin mesylate (Halaven®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Policy Guidelines

There is no Medicare coverage determination addressing eribulin mesylate (Halaven®); therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, eribulin mesylate (Halaven®) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

Certain drugs are available either under the member's medical benefit (Part B benefit) or under the member's pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when eribulin mesylate (Halaven®) is covered under a member's medical benefit (Part B benefit). It does not address instances when eribulin mesylate (Halaven®) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Eribulin mesylate (Halaven®) was approved by the FDA on November 15, 2010 for treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or the metastatic setting.

Eribulin mesylate (Halaven®) was approved by the FDA on January 28, 2016 for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.

Anthracyclines include:
  • Doxorubicin (Adriamycin®)
  • Epirubicin (Ellence®)
  • Doxorubicin (Doxil®)

Taxanes include:
  • Paclitaxel (Taxol®)
  • Docetaxel (Taxotere®)
  • Paclitaxel protein-bound particles for injectable suspension (albumin-bound) (Abraxane®)


Description

Eribulin mesylate (Halaven®) was approved by the US Food and Drug Administration (FDA) in November 2010 for the treatment of metastatic breast cancer after an individual has received at least two other chemotherapeutic regimens (including anthracycline and taxane agents). In January 2016, eribulin mesylate (Halaven®) was approved for the treatment of unresectable or metastatic liposarcoma in individuals who have received a prior anthracycline-containing regimen. Eribulin mesylate (Halaven®) works by blocking the growth and division cycles of cancerous cells, resulting in cell death.

The safety and efficacy of eribulin mesylate (Halaven®) was evaluated in an open-label, randomized, multicenter study called Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus Eribulin (EMBRACE). This study involved 762 individuals with metastatic breast cancer who received at least two chemotherapeutic agents for the treatment of metastatic disease and had experienced disease progression within 6 months of their last treatment. Prior therapy included anthracycline and taxane agents for adjuvant or metastatic disease. Individuals were randomized to receive eribulin mesylate (Halaven®) or another single agent consisting of chemotherapy or a hormonal agent (the control group). Randomization was stratified by geographic region, human epidermal growth factor receptor HER-2/neu status, and prior capecitabine exposure. The results showed that those who received eribulin mesylate (Halaven®) survived a median of 2.5 months longer than those in the control group.

Overall survival in individuals with advanced or metastatic soft tissue sarcoma was evaluated in a open-label, randomized, multicenter, phase 3 study. The study involved a total of 450 individuals, 227 receiving eribulin and 223 receiving dacarbazine, aged 18 years or older with intermediate or high grade advanced liposarcoma or leiomyosarcoma who had received at least 2 previous systemic regimens. Individuals were randomized to receive eribulin or dacarbazine, which was stratified by disease type (liposarcoma or leiomyosarcoma), region and the number of previous regimens (two or more than two). The results showed a 2 month survival advantage in the eribulin group which was found to be statistically significant and clinically relevant.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

American Hospital Formulary Service--Drug Information (AHFS-DI). Eribulin mesylate. [LexiComp Web site]. 02/27/2018. Available at: http://online.lexi.com/lco/action/home [via subscription only]. liAccessed November 07, 2018.

Clinical Pharmacology. Eribulin mesylate. 2018. Available at https://www.clinicalkey.com/pharmacology/. Accessed November 07, 2018.

Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomized study. Lancet. 2011; 377(9769):914-923.

Cortes J, Vahdat L, Blum JL, et al. Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2010; 28(25):3922-3928.

Eisai, Inc. Full Prescribing Information for Halaven® (eribulin mesylate) injection. Woodcliff Lakes, NJ. Eisai, Inc. Website. October 2016. Available at: http://www.halaven.com/hcp/sites/default/files/HALAVEN-Full-Prescribing-Information-2015.pdf. Accessed November 07, 2018.

Lexi-Drugs. Eribulin mesylate. [Lexicomp Web site]. 10/31/2018. Available at http://online.lexi.com/lco/action/search?q=eribulin&t=name. Accessed November 07, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Breast cancer. Version 3.2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed November 07, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Soft tissue sarcoma. Version 2.2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf. Accessed November 07, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Uterine neoplasms. Version 1.2019. Available at: http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed November 07, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Eribulin. [National Comprehensive Cancer Network Web site]. 2018. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=385 [via subscription only]. Accessed
November 07, 2018.

Schoffski P, Chawla S, Maki R, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: randomised, open-label, multicentre, phase 3 trial. Lancet. 2016; 387:1629-1637.

Truven Health Analytics Inc. Micromedex® 2.0 Healthcare Series. DrugDex®. Eribulin. [Micromedex Web site]. 2018. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed November 07, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Halaven®. [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/. Accessed November 07, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Eribulin mesylate (Halaven®). Package insert. [FDA Web site]. August 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201532s006lbl.pdf . Accessed November 07, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Eribulin mesylate (Halaven®). Approval letter. [FDA Web site]. 11/15/2010. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/201532s000ltr.pdf. Accessed November 07, 2018.

Vahdat LT, Pruitt B, Fabian CJ, et al. Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2009; 27(18):2954-2961.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A


HCPCS Level II Code Number(s)

J9179 Injection, eribulin mesylate, 0.1mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Eribulin Mesylate (Halaven®)
Description: ICD-10 Codes and Narratives






Policy History

MA08.056c
12/04/2019This policy has been reissued in accordance with the Company's annual review process.
03/25/2019 This version of the policy will become effective 03/25/2019.

In accordance with National Comprehensive Cancer Network Drugs and Biologics Compendium, the Company’s coverage position for Eribulin mesylate (Halaven®) has changed from Medically Necessary to Experimental/Investigational for uterine neoplasms-uterine sarcoma.

For soft tissue sarcoma, the following medically necessary coverage for Eribulin mesylate (Halaven®) was added:
  • Single-agent palliative chemotherapy for individuals with synchronous stage IV or recurrent disease of the head/neck
  • Single-agent palliative chemotherapy for individuals with liposarcoma

The following ICD-10 CM codes have been deleted from this policy:
    C54.0 Malignant neoplasm of isthmus uteri
    C54.1 Malignant neoplasm of endometrium
    C54.2 Malignant neoplasm of myometrium
    C54.3 Malignant neoplasm of fundus uteri
    C54.8 Malignant neoplasm of overlapping sites of corpus uteri
    C54.9 Malignant neoplasm of corpus uteri, unspecified
    C55 Malignant neoplasm of uterus, part unspecified

Revisions from MA08.056b
03/08/2017 This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Coverage was added for the condition of unresectable or metastatic liposarcoma with criteria. Criteria was updated for the condition of uterine sarcoma.

Revisions from MA08.056a
12/30/2015This version of the policy will become effective 12/30/2015.

The following updates were made to the medical necessity criteria for single-agent treatment of eribulin mesylate (Halaven®) for individuals with breast cancer:
  • Specified the type of breast cancer as 'invasive'
  • Modified the following criteria for single-agent treatment for individuals with recurrent or metastatic human epidermal growth factor receptor 2-negative (HER-2) invasive breast cancer:
    • FROM: Hormone receptor--positive, Human epidermal growth factor receptor 2 (HER-2)--negative with visceral crisis
    • TO: Human epidermal growth factor receptor 2 (HER-2)--negative with symptomatic visceral disease or visceral crisis
  • Removed the following indications:
    • HER-2--positive and endocrine therapy--refractory
      • HER2-positive individuals should have previously received anti-HER-2 treatments (such as Herceptin or Tykerb), unless they are ineligible due to inadequate cardiac function.
    • Progressive with no clinical benefit after three consecutive endocrine therapy regimens or with symptomatic visceral disease
  • Added the following indication:
    • Therapy in combination with trastuzumab (Herceptin®) for HER 2-positive recurrent or metastatic trastuzumab (Herceptin®)-exposed invasive breast cancer that is either of the following:
      • With symptomatic visceral disease or visceral crisis
      • That is either hormone receptor-negative or hormone receptor-positive and endocrine therapy refractory

Soft tissue sarcoma and uterine sarcoma were added as medically necessary indications.

The following updates were made to the coding table:
  • Removed ICD-9 diagnosis codes
  • Added ICD-10 codes for soft tissue sarcoma and uterine sarcoma
  • Removed ICD-10 diagnosis code Z85.3 (Personal history of malignant neoplasm of the breast)

Revisions from MA08.056
01/01/2015This is a new policy.





Version Effective Date: 03/25/2019
Version Issued Date: 03/25/2019
Version Reissued Date: 12/05/2019