Coverage Policy Manual
Policy #: 2021011
Category: Pharmacy
Initiated: June 2021
Last Review: March 2025
  Eribulin mesylate (e.g., HALAVEN)
Description:
Eribulin mesylate (e.g., HALAVEN), a microtubule inhibitor, inhibits the growth phase of microtubules without affecting the shortening phase and isolates tubulin into nonproductive aggregates. Eribulin mesylate exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. Eribulin mesylate is approved for the treatment of metastatic breast cancer and unresectable or metastatic liposarcoma. (Halaven, 2016)
 
The National Comprehensive Cancer Network® (NCCN) includes additional off-label category 2A recommendations for the use of eribulin mesylate. Recommendations include use for soft tissue sarcoma of the extremity/body wall or head/neck, retroperitoneal/intra-abdominal soft tissue sarcoma, advanced or metastatic pleomorphic rhabdomyosarcoma, solitary fibrous tumor, and angiosarcoma. Please refer to the NCCN guidelines for NCCN 1 and 2A recommendations.
 
Regulatory Status
 
Eribulin mesylate (e.g., Halaven) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of individuals with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease and for unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
The Step Therapy Medication Act is applicable to fully insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective August 1, 2021, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service and is managed through the oncology benefits management program.
 
Effective March 12, 2025
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Eribulin mesylate (e.g., HALAVEN) meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met for each indication:
 
For FDA labeled indications, Eribulin mesylate (e.g., HALAVEN) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.
 
For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication in the dosage and administration section.
 
FDA Labeled Indications:
 
The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication below with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”)].
 
For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.
 
STANDARD REVIEW for up to 12 months:
 
1. Individual is age 18 years of age or older (Halaven, 2016); AND
2. Individual has a diagnosis of metastatic breast cancer (Halaven, 2016); AND
a. Individual has received at least two chemotherapeutic regimens for the treatment of metastatic disease: Prior therapy should have included an anthracycline (e.g., doxorubicin, epirubicin) and a taxane (e.g., docetaxel, paclitaxel, nab-paclitaxel) in either the adjuvant or metastatic setting (Halaven, 2016); OR
3. Individual has a diagnosis of unresectable or metastatic liposarcoma(Halaven, 2016); AND
a. Individual has received a prior anthracycline-containing regimen (Halaven, 2016).
 
Off-label Indications:
 
The use of this drug for off-label indications not listed below is subject to policy 2000030.
 
STANDARD REVIEW for up to 12 months:
 
The following indications are covered when the individual meets the related NCCN category 1 or 2A recommendations specific to the indications below (e.g., histology, cancer staging, surgical status, mono- or combination therapy, and previous lines of therapy):
 
1. Soft Tissue Sarcoma:
a. Extremity/Body Wall, Head/Neck (NCCN 1 and 2A); OR
b. Retroperitoneal/Intra-Abdominal (NCCN 1 and 2A); OR
c. Rhabdomyosarcoma (NCCN 2A); OR
2. Breast Cancer:
a. Invasive Breast Cancer (NCCN 1 and 2A); OR
b. Inflammatory Breast Cancer (NCCN 2A).
 
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications.
 
Dosage and Administration
Dosing per FDA Guidelines unless otherwise specified below.
 
The recommended dose of eribulin mesylate 1.4mg/square meters administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
 
Eribulin mesylate is available as a 1mg/2mL vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eribulin mesylate (e.g., HALAVEN), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, eribulin mesylate for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 2024 to March 11, 2025
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Eribulin mesylate (e.g., HALAVEN) meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met for each indication:
 
Metastatic Breast Cancer [FDA, Halaven  2016; NCCN 2A]
1. Individual is diagnosed with locally recurrent or metastatic breast cancer; AND
2. Individual is 18 years of age or older; AND
3. Individual has received at least two previous chemotherapy regimens for locally recurrent or metastatic breast cancer; AND
a. One therapy must have included a taxane; AND
b. One therapy must have included an anthracycline; AND
4. One of the following:
a. Individual is HER2-negative and will be taking as monotherapy OR  is HER2-positive and will be taking in combination with trastuzumab; AND
5. Must be dosed in accordance with the FDA label.
 
OR
 
Soft Tissue Sarcoma  [FDA, Halaven  2016; NCCN 1-2A]
1. Individual is diagnosed with one of the following:
a. Locally recurrent, locally advanced, or metastatic liposarcoma; OR
b. Angiosarcoma (palliative); OR
c. Solitary fibrous tumor; OR
d. Advanced or metastatic pleomorphic rhabdomyosarcoma; OR
e. Soft tissue sarcoma of the extremity/body wall or head/neck; OR
f. Retroperitoneal/intra-abdominal soft tissue sarcoma; AND
2. Individual is 18 years of age or older; AND
3. Individual has received at least two prior systemic chemotherapy regimens (one therapy must have included an anthracycline); AND
4. Must be dosed in accordance with the FDA label.
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of eribulin mesylate 1.4mg/square meters administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
 
Eribulin mesylate is available as a 1mg/2mL vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eribulin mesylate (e.g., HALAVEN), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of eribulin mesylate for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 2023 to February 2024
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
Eribulin mesylate (e.g., HALAVEN) meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for metastatic breast cancer and unresectable or metastatic liposarcoma when dosed in accordance with FDA labeling and ALL of the  following numbered criteria are met for each indication.
 
Metastatic Breast Cancer [FDA, Halaven  2016; NCCN 2A]
    1. Individual is diagnosed with locally recurrent or metastatic breast cancer AND
    2. Individual is 18 years of age or older AND
    3. Individual has received at least two previous chemotherapy regimens for locally recurrent or metastatic breast cancer AND
a. One therapy must have included a taxane AND
b. One therapy must have included an anthracycline AND
4. One of the following:
a. Individual is HER2-negative and will be taking as monotherapy OR  is HER2-positive and will be taking in combination with trastuzumab.
5. Must be dosed in accordance with the FDA label.
 
OR
 
Soft Tissue Sarcoma  [FDA, Halaven  2016; NCCN 1-2A]
    1. Individual is diagnosed with one of the following:
a. Locally recurrent, locally advanced, or metastatic liposarcoma OR
b. Angiosarcoma (palliative) OR
c. Solitary fibrous tumor OR
d. Advanced or metastatic pleomorphic rhabdomyosarcoma OR
e. Soft tissue sarcoma of the extremity/body wall or head/neck OR
f. Retroperitoneal/intra-abdominal soft tissue sarcoma AND
2. Individual is 18 years of age or older AND
3. Individual has received at least two prior systemic chemotherapy regimens (one therapy must have included an anthracycline).
4. Must be dosed in accordance with the FDA label.
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of eribulin mesylate 1.4mg/square meters administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
 
Eribulin mesylate is available as a 1mg/2mL vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eribulin mesylate does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any indication or circumstance other than those outlined above.
 
For members with contracts without primary coverage criteria, the use of eribulin mesylate in any condition or circumstance other than listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
EFFECTIVE JANUARY 1, 2022 to February 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of eribulin mesylate meets primary coverage criteria for metastatic breast cancer and unresectable or metastatic liposarcoma when dosed in accordance with FDA labeling and ALL of the  following numbered criteria are met for each indication.
 
Metastatic Breast Cancer [FDA, Halaven  2016; NCCN 2A]
        1. Member is diagnosed with locally recurrent or metastatic breast cancer AND
        2. Member is 18 years of age or older AND
        3. Member has received at least two previous chemotherapy regimens for locally recurrent or metastatic breast cancer AND
                1. One therapy must have included a taxane AND
                2. One therapy must have included an anthracycline AND
        4. One of the following:
                1. Member is HER2-negative and will be taking as monotherapy OR
                2. Member is HER2-positive and will be taking in combination with trastuzumab.
OR
 
Soft Tissue Sarcoma  [FDA, Halaven  2016; NCCN 1-2A]
        1. Member is diagnosed with one of the following:
                1. Locally recurrent, locally advanced, or metastatic liposarcoma OR
                2. Angiosarcoma (palliative) OR
                3. Solitary fibrous tumor OR
                4. Advanced or metastatic pleomorphic rhabdomyosarcoma OR
                5. Soft tissue sarcoma of the extremity/body wall or head/neck OR
                6. Retroperitoneal/intra-abdominal soft tissue sarcoma AND
        2. Member is 18 years of age or older AND
        3. Member has received at least two prior systemic chemotherapy regimens (one therapy must have included an anthracycline).
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
 
The recommended dose of eribulin mesylate 1.4mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
 
Eribulin mesylate is available as a 1mg/2mL vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eribulin mesylate does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, the use of eribulin mesylate in any other condition than listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective June 1, 2021 - December 31, 2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of eribulin mesylate meets primary coverage criteria for metastatic breast cancer and unresectable or metastatic liposarcoma when dosed in accordance with FDA labeling and ALL of the  following numbered criteria are met for each indication
 
Metastatic Breast Cancer
    1. Member is diagnosed with metastatic breast cancer AND
    2. Member is 18 years of age or older AND
    3. Member has received at least two previous chemotherapy regimens for locally recurrent or metastatic breast cancer AND
        1. One therapy must have included a taxane AND
        2. One therapy must have included an anthracycline AND
    4. One of the following:
        1. Member is HER2-negative and will be taking as monotherapy OR
        2. Member is HER2-positive and will be taking in combination with trastuzumab AND
    5. Member has a current ECOG performance status of 2 or lower
 
OR
 
Soft Tissue Sarcoma
    1. Member is diagnosed with one of the following:
        1. Locally recurrent, locally advanced, or metastatic liposarcoma OR
        2. Angiosarcoma OR
        3. Solitary fibrous tumor OR
        4. Advanced or metastatic pleomorphic rhabdomyosarcoma OR
        5. Soft tissue sarcoma of the extremity/body wall or head/neck OR
        6. Retroperitoneal/intra-abdominal soft tissue sarcoma AND
    2. Member is 18 years of age or older AND
    3. Member has received at least two prior systemic chemotherapy regimens (one therapy must have included an anthracycline) AND
    4. Member has a current ECOG performance status of 2 or lower
 
The ECOG or Eastern Cooperative Oncology Group Performance Status is based on the following scale:
    • 0 = Fully active, able to carry on all pre-disease performance without restriction
    • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work
    • 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
    • 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
    • 5 = Dead
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
 
The recommended dose of eribulin mesylate 1.4mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
 
Eribulin mesylate is available as a 1mg/2mL vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eribulin mesylate does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, the use of eribulin mesylate in any other condition than listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
The safety and efficacy of eribulin mesylate for the treatment of metastatic breast cancer was studied in an open-label, randomized, multicenter, phase 3 trial. 762 patients with metastatic breast cancer who had previously received at least two chemotherapeutic regimens for adjuvant or metastatic disease and had an ECOG score of 2 or less were included in the trial. Prior chemotherapies must have included an anthracycline and taxane. Patients received eribulin mesylate (n=508) 1.4 mg/m² administered intravenously during 2–5 min on days 1 and 8 of a 21-day cycle or treatment of physician’s choice (n=254). Physician’s choice included both chemotherapy and hormone therapy regimens. Treatment was continued until disease progression, unacceptable toxicity, patient or physician request to discontinue, or serious protocol non-compliance. A statistically significant improvement in overall survival was observed in patients receiving eribulin mesylate compared to patients receiving treatment of physician’s choice, median overall survival was 13.1 months vs 10.6 months, respectively. The median duration of treatment in the eribulin mesylate arm was 3.9 months (range 0.7–16.3). The median duration of treatment of physician’s choice was 2.1 months (range 0.03–21.2) for patients receiving chemotherapy (n=238), and 1.0 month (range 0.8–6.2) with hormone therapy (n=9). Adverse events occurred in 99% of the patients receiving eribulin mesylate and in 93% of patients given treatment of physician’s choice. The most common adverse events in patients who received eribulin mesylate were fatigue, neutropenia, leucopenia, and peripheral neuropathy. Serious adverse events occurred in 25% of patients receiving eribulin mesylate and in 26% of patients given treatment of physician’s choice. (Cortes, 2011)
 
The safety and efficacy of eribulin mesylate for the treatment of liposarcoma was studied in an open-label, multicenter, active-controlled trial. 446 patients with unresectable, locally advanced or metastatic liposarcoma who had previously received at least two prior systemic chemotherapies (one of which must have included an anthracycline) were included in the trial. Patients were randomized to eribulin mesylate 1.4mg/m2 administered intravenously on Days 1 and 8 of a 21-day cycle or to dacarbazine at a dose of 850 mg/m2, 1,000 mg/m2, or 1,200 mg/m2 administered intravenously every 21 days. The dacarbazine dose was selected by the investigator prior to randomization. Treatment was continued until disease progression or unacceptable toxicity. In all patients, eribulin mesylate indicated a statically significant improvement in overall survival versus dacarbazine. Medial overall survival was 13.5 months in patients treated with eribulin mesylate and median overall survival was 11.3 months in patients treated with dacarbazine. There was no significant different in progression-free survival. Adverse events occurred in 99% of patients receiving eribulin mesylate and in 97% of patients receiving dacarbazine. Neutropenia and leukopenia were more common in patients given eribulin mesylate, whereas anaemia and thrombocytopenia were more common in those given dacarbazine. (Patrick, 2011)
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2025.
CPT/HCPCS:
J9179Injection, eribulin mesylate, 0.1 mg
References: Cortes J, O’Shaughnessy J, Loesch D, et al.(2011) Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomized study. The Lancet. 2011 Mar 12;377(9769):914-23.

Halaven [package insert]. Woodcliff Lake, NJ; Eisai Inc. 2016

Kaufman PA, Awada A, Twelves C, et al.(2015) Phase III open-label randomized study of eribulin mesylate verses capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. Journal of Clinical Oncology. 2015;33:594-601.

NCCN Clinical Practice Guidelines in Oncology™(2021) © 2020 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on February 22, 2021. Breast Cancer. V1.2021. Revised January 15, 2021.

NCCN Clinical Practice Guidelines in Oncology™.(2020) © 2020 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on February 22, 2021. Soft Tissue Sarcoma. V1.2021. Revised October 30, 2020.

Patrick S, Sant C, Robert GM, et al.(2011) Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomized, open-label, multicenter, phase 3 trial. Lancet Oncology. 2011;12(11):1045-1052.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.