Description

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.

Criteria

Coverage is subject to the specific terms of the member’s benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

The use of trastuzumab (Herceptin) may be considered medically when the presence of the HER2-overexpression 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 ); or 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) may be considered medically necessary for ANY of the following indications:

Food and Drug Administration (FDA) 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.

The use of trastuzumab (Herceptin) for any other indication listed above is considered experimental/investigational, and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Trastuzumab (Herceptin) may be considered medically necessary for ANY of the following:

National Comprehensive Cancer Network (NCCN) Recommendations

Endometrial Carcinoma

• When used in combination with carboplatin and paclitaxel for advanced stage III/IV and recurrent HER2-positive uterine serous carcinoma; or

 Esophageal and Esophagogastric Junction Cancers

• For use as palliative therapy for the treatment of individuals with HER2 overexpressing metastatic adenocarcinoma and Karnofsky performance score equal to or greater than 60% or Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2 as first-line therapy in combination with systemic chemotherapy
  • Note: not recommended for use with anthracyclines; or

  Gastric Cancer

• For use as palliative therapy for the treatment of individuals with HER2 overexpressing metastatic adenocarcinoma and Karnofsky performance score equal to or greater than 60% or ECOG performance score of less than or equal to 2 as first-line therapy in combination with systemic chemotherapy:
  • Note: not recommended for use with anthracyclines; or

Invasive Breast Cancer

• As preoperative systemic therapy for individuals with HER2-positive tumors and clinical stage T0-1, N1, M0 or T2-3, N0-1, M0 disease who desire breast preservation and fulfill criteria for breast-conserving surgery except for tumor size, or for those who have node-positive disease likely to become node-negative with preoperative systemic therapy, or for locally advanced clinical stage T0-3, N2, M0; T4, N0-2, M0 or any T, N3, M0 disease in ANY of the following:
  • In combination with paclitaxel with or without pertuzumab following AC (doxorubicin and cyclophosphamide) regimen; or
  • As a component of TCH (docetaxel, carboplatin, and trastuzumab) regimen with or without pertuzumab; or
  • In combination with docetaxel with or without pertuzumab following AC regimen; or
  • In combination with docetaxel and cyclophosphamide; or
• As adjuvant systemic therapy* for individuals with HER2-positive tumors and clinical stages T1-3, N0, M0 or RT0-3, N1, M0 disease, or for locally advanced clinical stage T0-3, N2, M0; T4, N0-2, M0 disease or any T, N3, M0 disease in ANY of the following:
  • In combination with paclitaxel following AC regimen; or
  • As a component of TCH regimen; or
  • In combination with docetaxel following AC regimen; or
  • In combination with docetaxel and cyclophosphamide; or
  • As a component of TCH regimen with pertuzumab for node positive tumors; or
  • In combination with paclitaxel for low-risk T1, N0, M0, HER2-positive tumors particularly for individuals not eligible for other standard adjuvant regimens due to comorbidities; or
• When used in combination with tamoxifen, fulvestrant, or aromatase inhibition with or without lapatinib, for the treatment of recurrent or stage IV (M1) hormone receptor-positive non-visceral or asymptomatic visceral HER2-positive disease in EITHER of the following:
  • Postmenopausal women** or premenopausal women treated with ONE of the following:
    • Ovarian ablation/suppression if prior endocrine therapy within one (1) year; or
    • With or without ovarian ablation/suppression if no prior endocrine  therapy within one (1) year; or
• When used for recurrent or stage IV (M1) HER2-positive disease that is either hormone receptor-negative, hormone receptor-positive and endocrine therapy refractory, with symptomatic visceral disease, or visceral crisis in ANY of the following:
  • As first-line therapy in combination with pertuzumab with docetaxel or paclitaxel; or
  • In combination with docetaxel, vinorelbine, or capecitabine or with paclitaxel with or without carboplatin; or
  • In combination with carboplatin, cisplatin, cyclophosphamide, eribulin, gemcitabine, ixabepilone, lapatinib (without cytotoxic therapy) or albumin-bound paclitaxel; or
  • In combination with pertuzumab with or without cytotoxic therapy (eg, vinorelbine or taxane) for one line of therapy beyond first-line therapy in individuals previously treated with chemotherapy and trastuzumab in the absence of pertuzumab; or

Leptomeningeal Metastases

• For use as intra-cerebrospinal fluid (CSF) treatment for leptomeningeal metastases from breast cancer for ANY of the following:
  • Primary treatment in individuals with normal CSF flow or no clinical evidence of abnormal flow; or
  • Maintenance treatment in individuals with negative CSF cytology or in clinically stable individuals with persistently positive CSF cytology; or
  • Treatment in individuals with positive CSF cytology; or

Salivary Gland Tumors

• For treatment for HER2-positive recurrent disease with distant metastases in individuals with a performance status (PS) 0-3.

The use of trastuzumab (Herceptin) for any other indication listed above is considered experimental/investigational, and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Trastuzumab-pkrb (Herzuma®) may be considered medically necessary for ANY of the following indications:

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
• 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.

Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

• For the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma in individuals who have not received prior treatment for metastatic disease.

The use of trastuzumab-pkrb (Herzuma) for any other indication listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Trastuzumab-anns (Kanjinti™) may be considered medically necessary for ANY of the following indications:

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

Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

• For the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma in individuals who have not received prior treatment for metastatic disease.

The use of trastuzumab-anns (Kanjinti) for any other indication listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Trastuzumab-dttb (Ontruzant®) may be considered medically necessary for ANY of the following indications:

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

Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

• For the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma in individuals who have not received prior treatment for metastatic disease.

The use of trastuzumab-dttb (Ontruzant) for any other indication listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Trastuzumab-dkst (Ogivri®) may be considered medically necessary for ANY of the following indications:

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 agnet 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

Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

• For the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma in individuals who have not received prior treatment for metastatic disease.

The use of trastuzumab-dkst (Ogivri) for any other indication listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

Trastuzumab-qyyp (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 (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

Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

• For the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma in individuals who have not received prior treatment for metastatic disease.

The use of trastuzumab-qyyp (Trazimera) for any other indication listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

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

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.

The use of trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) for any other indication listed above is considered experimental/investigational and therefore, not covered. The safety and/or efficacy cannot be established by review of the available published peer-reviewed literature.

Procedure Codes

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. Blue Cross Blue Shield of North Dakota may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

*Note: If no residual disease after preoperative therapy or no preoperative therapy, complete up to one year of HER2-targetted therapy with trastuzumab with or without pertuzumab after completing planned chemotherapy regimen course. If residual disease is present after preoperative therapy and ado-trastuzumab emtansine (Kadcyla™) is discontinued for toxicity, then trastuzumab with or without pertuzumab to complete one year of therapy can be used.

**Note: Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis.

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).

Diagnosis Codes

Covered Diagnosis Codes for Procedure Code J9355

Covered Diagnosis codes for Q5112, Q5113, Q5114, Q5116, Q5117

Covered Diagnosis Codes for J9356