In certain cancers, the human epidermal growth factor receptor 2 (HER2) gene is amplified and overexpressed. Trastuzumab (Herceptin®) is a humanized monoclonal antibody, HER2 receptor antagonist, used for the treatment of various cancers including breast and metastatic gastric or gastroesophageal junction adenocarcinoma works by halting the out-of-control growth prompted by an overabundance of the HER2/neugene.

Trastuzumab-pkrb (Herzuma®), trastuzumab-anns (Kanjinti™), trastuzumab-dttb (Ontruzant®), trastuzumab-dkst (Ogivri®), or trastuzumab-qyyp (Trazimera™) are biosimilars of trastuzumab (Herceptin).

Preferred Products

Trastuzumab-anns (Kanjinti) and trastuzumab-qyyp (Trazimera) are the preferred trastuzumab biosimilars for individuals initiating new therapy for oncologic indications when the clinical criteria within this policy are met. A non-preferred product will be considered when the individual has a documented therapy failure after an adequate therapeutic trial of a preferred product, or the preferred product has not been tolerated or is contraindicated.

Adequate therapeutic trial is defined as 180 days from first dose of therapy at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.

New therapy is defined as no previous utilization within the 180 last calendar days.

Non-Preferred Products

In order for a request for a non-preferred product [trastuzumab (Herceptin), trastuzumab and hyaluronidase-oysk (Herceptin Hylecta), trastuzumab-pkrb (Herzuma), trastuzumab-dttb (Ontruzant) or trastuzumab-dkst (Ogivri)] to be approved the individual must have had an adequate therapeutic trial and experienced a documented drug therapy failure or intolerance to the preferred product(s) or the preferred product is contraindicated.

Adequate therapeutic trial is defined as 180 days from first dose of therapy at Food and Drug Administration (FDA) or compendia based therapeutic doses of preferred product.

The use of trastuzumab (Herceptin) and trastuzumab biosimilars (Herzuma, Kanjinti, Ontruzant, Ogivri, Trazimera) may be considered medically necessary when the presence of the HER2-over expression is confirmed by the following:

HER2-overexpression must be verified by ANY ONE of the following FDA approved diagnostic tests:

• An immunohistochemical (IHC) assay with a result of 3+ (positive); or
• A positive fluorescence in situ hybridization (FISH) test (ratio greater than 2.0); or
• Single-probe in situ hybridization (ISH) test with average HER2  copy number 6.0 signals/cell or greater; or
• Dual-probe ISH test HER2/CEP17 (chromosome enumeration probe 17) ratio 2.0 or greater; or HER2/CEP17 ratio less than 2.0 AND average HER2 copy number 6.0 signals/cell or greater.

Confirmatory tests should be performed for borderline results as follows:

• If IHC assay has a result of 2+, confirm with ISH test of the same sample or a new test with IHC or ISH (if new sample available); or
• If FISH test has a HER2 gene/chromosome 17 ratio of 1.8-2.0, confirm with FISH re-test; additional cell counting and recalculation of the ratio; or IHC assay; or
• If single-probe ISH assay has an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with dual-probe ISH or with IHC (if same sample), or with a new ISH or IHC (if new sample available); or
• If dual-probe ISH assay has a HER2/CEP17 ratio less than 2.0 and an average HER2 copy number result of 4.0 to less than 6.0 signals/cell, confirm with one of the following: IHC (if same sample), alternative ISH chromosome 17 probe, or order a new test with ISH or IHC (if new sample available).

Trastuzumab (Herceptin) and trastuzumab biosimilars (Herzuma, Kanjinti, Ontruzant, Ogivri, Trazimera) may be considered medically necessary for ANY of the following indications:

 Breast Cancer

• For adjuvant treatment of HER2-overexpressing node positive or node negative (estrogen receptor/progesterone [ER/PR] receptor negative or with one high risk feature) breast cancer in ANY of the following:
  • As part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or
  • As part of a treatment regimen with docetaxel and carboplatin; or
  • As a single agent following multi-modality anthracycline based therapy; or
• For metastatic breast cancer in ANY of the following:
  • In combination with paclitaxel for first-line treatment of HER2-ovrexpressing metastatic breast cancer; or
  • As a single agent for treatment of HER2-overexpressing breast  cancer in individuals who have received one or more chemotherapy regimens for metastatic disease; or

Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

• For treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma in combination with cisplatin and capecitabine or 5-fluorouracil in individuals who have not received prior treatment for metastatic disease.

Compendia Sources

Trastuzumab (Herceptin) and trastuzumab biosimilars (Herzuma, Kanjinti, Ontruzant, Ogivri, Trazimera) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of trastuzumab (Herceptin) and trastuzumab biosimilars (Herzuma, Kanjinti, Ontruzant, Ogivri, Trazimera) for any other indication listed above is considered not medically necessary.

Trastuzumab and hyaluronidase-oysk (Herceptin Hylecta™) may be considered medically necessary for ANY of the following:

Breast Cancer

• For adjuvant treatment of HER2-overexpressing node positive or node negative (ER/PR negative or with one high risk feature) breast cancer in ANY of the following:
  • As part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or
  • As part of a treatment regimen with docetaxel and carboplatin; or
  • As a single agent following multi-modality anthracycline based therapy; or
• For metastatic breast cancer in ANY of the following:
  • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer; or
  • As a single-agent for treatment of HER2-overexpressing breast cancer in individuals who have received one or more chemotherapy regimens for metastatic disease; or

Compendia Sources

Trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) may be considered medically necessary for treatment of any of the current category 1, 2A, or 2B NCCN recommendations.

The use of trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) for any other indication listed above is considered not medically necessary.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits. 

Do not substitute trastuzumab (Herceptin, Herzuma, Kanjinti, Ogivri, Ontruzant, or Trazimera) or trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) for or with ado-trastuzumab emtansine (Kadcyla) or fam-trastuzumab deruxtecan-nxki (Enhertu).