CurrentCareSourcePolicy N/A

UTILIZATION MANAGEMENT MEDICAL POLICY

Policy Summary

PayerCareSource

PolicyUTILIZATION MANAGEMENT MEDICAL POLICY

Policy CodePolicy N/A

Change TypeRevised prior therapy requirement

Effective Date

Next Review Date

Key ActionPrior Authorization is recommended for Margenza; approve when criteria and dosing are met.

SourceLink

POLICY UPDATE CHANGES

The number of prior anti-HER2 regimens required was changed from two to three.

Annual revision and review date updated to 02/19/2025.

1FDA-approved indication(s) listed

>=3Required prior anti-HER2 regimens

15 mg/kg q3wMaximum dose and frequency

18+Minimum age

Coverage Summary & Scope

Defines prior authorization and medical-benefit coverage criteria, dosing, prescriber requirements, and exclusions for Margenza (margetuximab-cmkb) for treatment of HER2-positive recurrent or metastatic breast cancer in adults. Coverage is covered with criteria when the patient has recurrent or metastatic HER2-positive disease, is ≥ 18 years of age, has tried at least three anti-HER2 regimens (with at least one used for metastatic disease), the medication is used in combination with chemotherapy, and is prescribed by or in consultation with an oncologist. Dosing limit: up to 15 mg/kg administered intravenously no more frequently than once every 3 weeks.

Boxed warnings: Margenza carries boxed warnings for left ventricular dysfunction and embryo-fetal toxicity. Background context: Margenza is a HER2 receptor antagonist indicated in combination with chemotherapy for metastatic HER2-positive breast cancer in adults per FDA, and NCCN recommends use as fourth-line and beyond in recurrent unresectable or stage IV disease.

Recommended Authorization Criteria (FDA-Approved Indication)

Approval is recommended when ALL of the following are met:

ALL of the following

Patient has recurrent or metastatic disease
Patient has human epidermal growth factor receptor 2 (HER2)-positive disease
Patient has tried at least three anti-HER2 regimens>= 3 regimens
Policy was revised to change required number of prior anti-HER2 regimens from two to three.
At least one of the prior anti-HER2 regimens was used for metastatic diseaseat least 1 regimen used for metastatic disease
Patient is ≥ 18 years of age>= 18 years
Medication is used in combination with chemotherapy
Examples of chemotherapy: capecitabine, eribulin, gemcitabine, vinorelbine.
Medication is prescribed by or in consultation with an oncologist

Dosing / Quantity Limits

Approve when dosing meets the following:

Dose up to 15 mg/kg administered as an intravenous infusionup to 15 mg/kg, not more frequently than once every 3 weeks

Not more frequently than once every 3 weeks

Provider Actions & Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is recommended for medical-benefit coverage of Margenza. Approval is recommended when the policy's criteria and dosing are met. All approvals are provided for the duration noted by the payer; extended approvals are allowed if the patient continues to meet the criteria and dosing.

See Authorization Criteria and Dosing

Documentation Required

Prescriber Specialty Requirement

Margenza must be prescribed by or in consultation with a physician who specializes in the condition treated (oncologist).

Billing Rule

Dose Requests Outside Policy

Requests for doses outside the established dosing documented in this policy will be considered on a case-by-case basis by a clinician (Medical Director or Pharmacist).

Anti‑HER2 Regimen Examples (Informational)

Relevant example prior anti-HER2 regimens cited (informational)mixed

	Perjeta (pertuzumab) + trastuzumab + docetaxel
	Perjeta + trastuzumab + paclitaxel
	Kadcyla (ado-trastuzumab emtansine)
	Enhertu (fam-trastuzumab deruxtecan-nxki)
	Tukysa (tucatinib) + trastuzumab + capecitabine
	trastuzumab + lapatinib
	trastuzumab + docetaxel
	trastuzumab + vinorelbine
	Nerlynx (neratinib) + capecitabine

Margenza (margetuximab-cmkb) is indicated in combination with chemotherapy for the treatment of metastatic HER2-positive breast cancer in adults. Per the FDA-approved context, it is indicated for patients who have received two or more anti-HER2 regimens (at least one for metastatic disease); the policy was revised to require at least three prior anti-HER2 regimens. The NCCN Breast Cancer Guidelines (v1.2025) recommend Margenza as a Category 2A therapy for fourth-line and beyond treatment of recurrent unresectable or stage IV disease, to be used in combination with chemotherapy (examples: capecitabine, eribulin, gemcitabine, vinorelbine).

Boxed warnings: Margenza has boxed warnings for left ventricular dysfunction (may reduce left ventricular ejection fraction; discontinue for clinically significant decreases) and embryo-fetal toxicity (exposure can cause embryo-fetal harm; advise effective contraception).

"Anti-HER2 regimen" refers to therapies that target the HER2 receptor, including combinations cited in the policy such as pertuzumab + trastuzumab + taxane (Perjeta + trastuzumab + docetaxel or paclitaxel), ado-trastuzumab emtansine (Kadcyla), fam-trastuzumab deruxtecan (Enhertu), tucatinib + trastuzumab + capecitabine (Tukysa regimen), trastuzumab + lapatinib, trastuzumab + docetaxel, trastuzumab + vinorelbine, and neratinib + capecitabine.

Revision History

02/19/2025revisedLatest