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Last Review Date: 03/05/2024

Date of Origin: 04/03/2019

Dates Reviewed: 04/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 03/2021, 03/2022, 03/2023, 03/2024

1. Length of Authorization ¹

Coverage is provided for 6 months and may be renewed (unless otherwise specified).

• Adjuvant therapy may be authorized for a total of fifty-two (52) weeks.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Herceptin Hylecta (600 mg trastuzumab/10,000 units hyaluronidase) single-dose vial: 1 vial every 21 days

2. Max Units (per dose and over time) [HCPCS Unit]:

• 60 billable units every 21 days

3. Initial Approval Criteria ^1-5

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria

• Left ventricular ejection fraction (LVEF) is within normal limits prior to initiating therapy and will be assessed at regular intervals (e.g., every 3 months) during treatment; AND
• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
• Therapy will not be substituted with or for ado-trastuzumab emtansine (Kadcyla) or fam-trastuzumab deruxtecan-nxki (Enhertu); AND
• Therapy will not be used in combination with intravenous chemotherapy agents; AND
• Therapy will not be used in combination with trastuzumab (or any of its biosimilar products [e.g., Ogivri, Kanjinti, Trazimera, Herzuma, Ontruzant]) or pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo); AND

Breast Cancer^** † ¹

• Used as adjuvant therapy; AND
  • Used as a single agent following anthracycline-based therapy †; OR
• Used for metastatic disease; AND
  • Used as a single agent in patients who have received one or more prior chemotherapy regimens for metastatic disease †

v If confirmed using an immunotherapy assay-http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: cardiotoxicity (e.g., left ventricular dysfunction, cardiomyopathy, etc.), pulmonary toxicity (e.g., dyspnea, interstitial pneumonitis, etc.), neutropenia, severe administration-related reactions (e.g., hypersensitivity, anaphylaxis), etc.; AND
• Left ventricular ejection fraction (LVEF) within the previous 3 months as follows:
  • LVEF is within the institutional normal limits, and has not had an absolute decrease of  ≥ 16% from pre-treatment baseline; OR
  • LVEF is below the institutional lower limits of normal, and has not had an absolute decrease of  ≥ 10% from pre-treatment baseline; AND

Breast Cancer (adjuvant treatment)

• Patient has not exceeded a maximum of fifty-two (52) weeks of therapy

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9356 – Injection, trastuzumab, 10 mg and hyaluronidase-oysk; 1 billable unit = 10 mg

NDC:

• Herceptin  Hylecta 600 mg/10,000 units (providing 600 mg trastuzumab and 10,000 units hyaluronidase per 5 mL) single-dose vials: 50242-0077-xx

7. References

1. Herceptin Hylecta [package insert]. South San Francisco, CA; Genentech, Inc; February 2019. Accessed February 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) trastuzumab and hyaluronidase human. National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES^® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed February 2024.
3. Jackisch C, Stroyakovskiy D, Pivot X, et al. Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer: Final Analysis of the HannaH Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 May 1;5(5):e190339.
4. Gligorov J, Ataseven B, Verrill M, et al. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients. Eur J Cancer. 2017 Sep;82:237-246.
5. Pivot X, Verma S, Fallowfield L, et al. Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: Final analysis of the randomised, two-cohort PrefHer study. Eur J Cancer. 2017 Nov;86:82-90.
6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer 1.2024. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed February 2024.
7. Wolff AC, Hammond EH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 2018;36:2105-2122.
8. First Coast Service Options, Inc. Local Coverage Article: Billing and Coding: Trastuzumab – Trastuzumab Biologics (A56660). Centers for Medicare & Medicaid Services, Inc. Updated on 10/08/2021 with effective date of 10/01/2021. Accessed February 2024.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

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