Trastuzumab – Trastuzumab Biologics

This LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for Trastuzumab – Trastuzumab Biologics. Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for Trastuzumab – Trastuzumab Biologics and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site.

Internet Only Manual (IOM) Citations:

• CMS IOM Publication 100-02, Medicare Benefit Policy Manual
  • Chapter 1, Sections 30-30.1 Drugs and Biologicals
  • Chapter 15, Section 50.4.1 – 50.4.3 Approved Use of Drug
• CMS IOM Publication 100-04, Medicare Claims Processing Manual
  • Chapter 12, Section 30.5 Payment for codes for Chemotherapy Administration and Nonchemotherapy Injections and infusions
  • Chapter 17, Sections 10 Payment Rules for Drugs and Biologicals, 20 Payment Allowance Limit for Drugs and Biologicals Not Paid on a Cost or Prospective Payment Basis, and 40 Discarded Drugs and Biologicals
  • Chapter 23, Sections 20.9 - 20.96 National Correct Coding Initiative (NCCI)
• CMS IOM Publication 100-08, Medicare Program Integrity Manual
  • Chapter 13, Section 13.5.4 Reasonable and Necessary Provision in an LCD

Social Security Act (Title XVIII) Standard References:

• Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.
• Title XVIII of the Social Security Act, Section 1862(a)(7). This section excludes routine physical examinations.
• Title XVIII of the Social Security Act, Section 1833(e) states that no payment shall be made to any provider for any claim that lacks the necessary information to process the claim.

Trastuzumab – Trastuzumab Biologics

Trastuzumab is a monoclonal antibody, one of a group of drugs designed to attack specific cancer cells. Trastuzumab’s targets are cancer cells that overexpress an oncogene called HER2 or HER2/neu, which occurs in high numbers in about 25 to 30 percent of breast cancers. According to the National Comprehensive Cancer Network (NCCN), breast cancers can be categorized as being HER2 positive or HER2 negative. HER2-positive breast cancer is faster growing and considered more aggressive. Studies indicate that the drug trastuzumab (Herceptin) is effective in treatment of HER2-positive early stage breast cancer and HER2-positive metastatic breast cancer. Trastuzumab is not effective in the treatment of HER2-negative breast cancers. 

There are two methods of testing for HER2 tumor status in women with breast cancer: immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 test results are interpreted as follows:

• HER2 positive status is IHC 3+ or FISH positive
• HER2 negative status is IHC 0, 1+ or FISH negative
• A borderline IHC result of 2+ should be followed by performing a FISH test.
• A borderline FISH result of an average HER2 gene/chromosome 17 ratio of 1.8 to 2.2 (or an average of greater than 4 to less than 6 HER2 gene copies/cell) should be followed by one of the following:
  • Counting additional cells in the tissue sample
  • Retesting with FISH
  • Performing an IHC test

Results from both tests are used in the clinical setting, and the results of the tests influence treatment choices for women with breast cancer. The pathology laboratory where the HER2 testing is done should be accredited to perform such testing. It should have quality control procedures in place to ensure that the test is done correctly, and a quality assurance plan to validate (i.e., determine the accuracy of) the HER2 test results.

Covered Indications

Trastuzumab – Trastuzumab Biologics

Trastuzumab and its biologics are covered for Food and Drug Administration (FDA) approved labeled indications. Please see the FDA drug label for the FDA approved indications and dosages. This can be accessed at https://labels.fda.gov/.

Trastuzumab and its biologics will be considered medically necessary when provided for its FDA approved uses, as well as for the treatment of any of the following off-labeled indications:

For metastatic and non-metastatic breast cancer, trastuzumab and its biologics may be considered medically reasonable and necessary when incorporated into the adjuvant therapy in the following recommended uses by the NCCN Drugs and Biologics Compendium: 

1. Preoperative chemotherapy in combination with paclitaxel followed by FEC/CEF (fluorouracil, epirubicin, and cyclophosphamide) regimen with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive stage IIA, IIB, or T3, N1, M0 disease who desire breast preservation and fulfill criteria for breast-conserving surgery except for tumor size or for patients with locally advanced disease (stage IIIA, IIIB, or IIIC). 
2. Adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive, stage I, IIA, IIB, or T3, N1, M0 disease (ductal, lobular, mixed, or metaplastic histologies) that is node-positive, node-negative with tumor 0.5 cm or greater in hormone receptor-negative patients, or node-negative with tumor 0.6 to 1 cm, grade 2 or 3, or with unfavorable features or tumor greater than 1 cm in hormone receptor-positive patients, or for patients with locally advanced disease (stages IIIA, IIIB, or IIIC). 
   • concurrently with paclitaxel following AC (doxorubicin and cyclophosphamide) regimen as preferred regimen 
   • in TCH (docetaxel, carboplatin, and trastuzumab) regimen as preferred regimen 
   • in combination with docetaxel followed by FEC/CEF (fluorouracil, epirubicin, and cyclophosphamide) regimen 
   • following chemotherapy 
   • in combination with docetaxel following AC regimen 
3. Used in combination with aromatase inhibition for the treatment of recurrent or stage IV estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-positive disease in postmenopausal women* who have received no prior endocrine therapy within one year.

   *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.

4. Preferred regimen for patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer that is hormone receptor-negative or hormone receptor-positive and endocrine refractory and not characterized by bone or soft tissue involvement only or asymptomatic visceral disease as: 
   • first-line chemotherapy in combination with docetaxel, vinorelbine, or capecitabine or with paclitaxel with or without carboplatin 
   • treatment for trastuzumab-exposed HER2-positive disease in combination with lapatinib without cytotoxic therapy, with docetaxel, vinorelbine, or capecitabine, or with paclitaxel with or without carboplatin

The timing of therapy combination with other agents or regimen, dosage, and duration of therapy should be based on NCCN guidelines and the package insert.

Limitations

For limitations of use of trastuzumab and its biologics, please see the FDA drug label. This can be accessed at: https://labels.fda.gov/

As published in the CMS IOM Publication 100-08, Medicare Program Integrity Manual, Chapter 13, Section 13.5.4, an item or service may be covered by a contractor LCD if it is reasonable and necessary under the Social Security Act Section 1862 (a)(1)(A). Contractors shall determine and describe the circumstances under which the item or service is considered reasonable and necessary.

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Documentation Requirements

Please refer to the Local Coverage Article: Billing and Coding: Trastuzumab – Trastuzumab Biologics (A56660) for documentation requirements that apply to the reasonable and necessary provisions outlined in this LCD.

Utilization Guidelines

Please refer to the Local Coverage Article: Billing and Coding: Trastuzumab – Trastuzumab Biologics (A56660) for utilization guidelines that apply to the reasonable and necessary provisions outlined in this LCD.

First Coast Service Options, Inc. reference LCD number(s) – L29030, L29297, L29482

Clinical Pharmacology, Trastuzumab, 12/22/2009.

U.S. Food and Drug Administration, Department of Health and Human Services, Drugs @ FDA, October 2010.

U.S. Food and Drug Administration (FDA). Product information KANJINTI^TM (trastuzumab-anns). 2019. Accessed September 06, 2019.

U.S. Food and Drug Administration (FDA). Product information TRAZIMERA^TM (trastuzumab-qyyp). 2019. Accessed September 06, 2019.

1. Compendia-Based Drug Bulletin. (February 2007). The Association of Community Cancer Centers.
2. Herceptin® (trastuzumab) for injection, for intravenous use, U.S. Food and Drug Administration (FDA) label. (2017).  
3. National Comprehensive Cancer Network (2010). Invasive Breast Cancer. Clinical Practice Guidelines in Oncology – V.2.2010.
4. National Comprehensive Cancer Network (2017). Esophageal and Esophagogastric Junction Cancers. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Version 1.2017.
5. National Comprehensive Cancer Network (2017). Gastric Cancer. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Version 1.2017.
6. National Comprehensive Cancer Network (NCCN) Drugs & Biologics Compendium (2010).
7. Thomson Micromedex . USP DI Drug Information for the Health Care Professional. (2007).

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