Last Review Date: 06/05/2025

Date of Origin: 08/04/2020

Dates Reviewed: 08/2020, 09/2020, 01/2021, 03/2021, 03/2022, 03/2023, 03/2024, 06/2025

1. Length of Authorization ¹

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

• Neoadjuvant and adjuvant therapy may be authorized for a total of 1 year (up to 18 cycles).

2. Dosing Limits

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

• Initial Dose: 180 billable units x 1 dose
• Maintenance Dose: 120 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 ¹

• 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 used in combination with pertuzumab or any trastuzumab-based formulation; AND

• Therapy will not be substituted for or with pertuzumab or any trastuzumab-based formulation; AND

Breast Cancer † ‡  ^1-7

• Used as neoadjuvant therapy; AND
  • Patient has locally advanced, inflammatory, or early-stage disease; AND
  • Used in combination with chemotherapy; OR
• Used as adjuvant therapy; AND
  • Patient has locally advanced, pT2-3 and pN0, inflammatory, or node positive disease OR early stage disease at high risk of recurrence; OR
  • Used after completion of planned chemotherapy and following mastectomy or breast-conserving surgery; AND
    • Patient has ≥ ypT0N0 or pCR disease by axillary staging; OR
• Used for recurrent unresectable or metastatic disease OR inflammatory breast cancer with no response to preoperative systemic therapy; AND
  • Used as first-line therapy in combination with either paclitaxel or docetaxel; OR
  • Used as subsequent therapy with or without cytotoxic therapy ‡; AND
    • • • • Patient was previously treated with trastuzumab and chemotherapy; AND
          • Patient has not previously received pertuzumab

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
• Duration of authorization has not been exceeded (refer to section I); 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., hypertension, arrhythmias, left ventricular dysfunction, cardiac failure, cardiomyopathy), pulmonary toxicity (e.g., angioedema, interstitial pneumonitis, acute respiratory distress syndrome, etc.), neutropenia/febrile neutropenia, severe administration-related reactions (e.g., hypersensitivity reactions, anaphylaxis), etc.; AND
• Left ventricular ejection fraction (LVEF) obtained within the previous 3 months as follows:

• Neoadjuvant and adjuvant treatment of breast cancer: LVEF is ≥ 50% OR LVEF has had an absolute decrease of < 10% from pre-treatment baseline; OR
• All other indications: LVEF is > 45% OR LVEF is 40% to 45% and absolute decrease is < 10% from pre-treatment baseline

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9316 – Injection, pertuzumab, trastuzumab, and hyaluronidase-zzxf, per 10 mg; 1 billable unit = 10 mg

NDC(s):

• Phesgo (1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase per 15 mL) single-dose vial: 50242-0245-xx
• Phesgo (600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase per 10 mL) single-dose vial: 50242-0260-xx

7. References

1. Phesgo [package insert]. South San Francisco, CA; Genentech, Inc; November 2024. Accessed April 2025.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) pertuzumab, trastuzumab and hyaluronidase-zzxf. National Comprehensive Cancer Network, 2025. 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 April 2025.
3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer 4.2025. National Comprehensive Cancer Network, 2025. 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 May 2025.
4. 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.
5. Tan AR, Im SA, Mattar A, et al. Subcutaneous administration of the fixed-dose combination of trastuzumab and pertuzumab in combination with chemotherapy in HER2-positive early breast cancer: Primary analysis of the phase III, multicenter, randomized, open-label, two-arm FeDeriCa study [Abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD4-07.
6. O'Shaughnessy J, Sousa S, Cruz J, et al. PHranceSCa study group. Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study. Eur J Cancer. 2021 Jul;152:223-232. doi: 10.1016/j.ejca.2021.03.047. Epub 2021 Jun 16. PMID: 34147014.
7. Gennari A, André F, Barrios CH, et al.; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021 Dec;32(12):1475-1495. doi: 10.1016/j.annonc.2021.09.019. Epub 2021 Oct 19. PMID: 34678411.
8. Wolff AC, Hammond MEH, 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 Jul 10;36(20):2105-2122. doi: 10.1200/JCO.2018.77.8738. Epub 2018 May 30. PMID: 29846122.

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.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A