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Last Review Date: 03/05/2024

Date of Origin: 11/01/2012

Dates Reviewed: 12/2012, 03/2013, 06/2013, 09/2013, 11/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020, 03/2021, 06/2021, 09/2021, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024

1. Length of Authorization ^1,2

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

• Neoadjuvant and adjuvant treatment in Breast Cancer may be authorized up to a maximum of 1 year of treatment [18 cycles].

2. Dosing Limits

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

Perjeta 420 mg/14 mL solution for injection:

• Loading Dose: 2 vials
• Maintenance Dose: 1 vial every 21 days

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

• Loading Dose: 840 billable units x 1 dose

• Maintenance Dose: 420 billable units every 21 days

3. Initial Approval Criteria ¹

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/trastuzumab and hyaluronidase-zzxf (Phesgo); AND

Breast Cancer † ‡ ^1-3,5-8,13

• Used as neoadjuvant or preoperative therapy; AND
  • Patient has locally advanced, node positive, or inflammatory disease; AND
  • Used in combination with trastuzumab and chemotherapy; OR
• Used as adjuvant therapy; AND
  • Patient has locally advanced, node positive, or inflammatory disease; AND
    • • • Used in combination with trastuzumab and chemotherapy; OR
        • Used in combination with trastuzumab; 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 trastuzumab AND either paclitaxel or docetaxel; OR
        • Used as subsequent therapy in combination with trastuzumab with or without cytotoxic therapy ‡; AND

• • • • • Patient was previously treated with trastuzumab and chemotherapy; AND
        • Patient has not previously received pertuzumab

Central Nervous System (CNS) Cancers ‡ ²

• Used for the treatment of brain metastases in patients with breast cancer; AND
• Used in combination with trastuzumab; AND
  • Used as initial treatment in patients with small asymptomatic brain metastases; OR
  • Used for relapsed limited brain metastases with either stable systemic disease or reasonable systemic treatment options; OR
  • Patient has recurrent limited brain metastases; OR
  • Used for recurrent extensive brain metastases with stable systemic disease or reasonable systemic treatment options

Colorectal Cancer (CRC) ‡ ^2,9-12

• Used for RAS and BRAF wild-type (WT) disease in combination with trastuzumab; AND
  • Used as initial treatment for unresectable metastatic disease and previous FOLFOX or CapeOX within the past 12 months; AND
    • • • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR
  • Used as primary treatment for unresectable (or medically inoperable), or metastatic disease if intensive therapy is not recommended; AND
    • • Patient has not previously received HER2-targeted therapy; AND
      • Used in one of the following:
    • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta [POLE/POLD1] mutation; AND
      •  Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy; OR
  • Used as primary treatment for T3, N Any; T1-2, N1-2; T4, N Any; or unresectable (or medically inoperable) rectal cancer if intensive therapy is not recommended; AND
    • Used if resection is contraindicated following total neoadjuvant therapy; AND
      • Patient has proficient mismatch repair/microsatellite-stable (pMMR/MSS) disease; OR
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta (POLE/POLD1) mutation; AND
        • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy; OR
    • Used if resection is contraindicated following neoadjuvant/definitive immunotherapy; AND
      • Patient has deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) disease; OR
  • Used as subsequent therapy for progression of advanced or metastatic disease; AND

• • • • Patient has not previously received HER2-targeted therapy; AND
      • Used in one of the following:
    • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR
    • Patient has mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta [POLE/POLD1] mutation; AND
      •  Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy

Appendiceal Adenocarcinoma – Colon Cancer ‡ ^2,10

• Used for RAS and BRAF wild-type (WT) disease in combination with trastuzumab; AND
• Patient has not previously received HER2-targeted therapy; AND
• Used for one of the following:
  • Used as initial therapy for advanced or metastatic disease if intensive therapy is not recommended; OR
  • Used as subsequent therapy for progression of advanced or metastatic disease; AND
• Used in one of the following:
  • Patient has mismatch repair proficient/microsatellite-stable (pMMR/MSS) disease; OR
  • Patient has mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) disease or polymerase epsilon/delta [POLE/POLD1] mutation; AND
    • Patient is not eligible for or has progressed on checkpoint inhibitor immunotherapy

Head and Neck Cancers ‡ ^2,14,15

• Patient has salivary gland tumors; AND
• Used in combination with trastuzumab; AND
• Used for one of the following:
  • Recurrent disease with distant metastases
  • Unresectable locoregional recurrence with prior radiation therapy (RT)
  • Unresectable second primary with prior RT

Biliary Tract Cancers (Gallbladder Cancer or Intra-/Extra-Hepatic Cholangiocarcinoma) ‡ ^2,16,17

• Used as subsequent treatment for progression on or after systemic treatment for unresectable, resected gross residual (R2), or metastatic disease; AND
• Used in combination with trastuzumab

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: left ventricular dysfunction, severe infusion-related reactions, 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 baseline
  • All other indications: LVEF is > 45% OR LVEF is 40% to 45% and absolute decrease is < 10% from baseline

Breast Cancer (neoadjuvant or adjuvant therapy) ^1,2

• Patient has not exceeded a maximum of 1 year of treatment (total of 18 cycles)

5. Dosage/Administration ^{1,10-13,15,16,18}

6. Billing Code/Availability Information

HCPCS Code:

• J9306 – Injection, pertuzumab, 1 mg; 1 mg = 1 billable unit

NDC:

• Perjeta 420 mg/14 mL single-dose vial for injection: 50242-0145-xx

7. References

1. Perjeta [package insert]. South San Francisco, CA; Genentech, Inc.; February 2021. Accessed January 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) pertuzumab. 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 January 2024.
3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer, Version 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 January 2024.
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. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32.
6. Baselga J, Cortes J, Kim SB, et al. CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109-119.
7. Schneeweiss A., Chia S., Hickish T., et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24 (9): 2278-2284.
8. von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017;377(2):122-131.
9. Hainsworth JD, Meric-Bernstam F, Swanton C, et al. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. Clin Oncol. 2018 Feb 20;36(6):536-542.
10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Colon Cancer, Version 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 January 2024.
11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Rectal Cancer, Version 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 January 2024.
12. Meric-Bernstam F, Hurwitz H, Raghav KPS, et al. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019;20(4):518-530. doi:10.1016/S1470-2045(18)30904-5.
13. Swain SM, Ewer MS, Viale G, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018;29(3):646-653. doi:10.1093/annonc/mdx773.
14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Head and Neck Cancer, Version 2.2024. 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 January 2024.
15. Kurzrock R, Bowles DW, Kang H, et al. Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study. Ann Oncol. 2020;31(3):412-421.
16. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021 Sep;22(9):1290-1300. doi: 10.1016/S1470-2045(21)00336-3. Epub 2021 Jul 30.
17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Biliary Tract Cancers, Version 3.2023. 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 January 2024.
18. Lin NU, Pegram M, Sahebjam S, et al. Pertuzumab Plus High-Dose Trastuzumab in Patients With Progressive Brain Metastases and HER2-Positive Metastatic Breast Cancer: Primary Analysis of a Phase II Study. J Clin Oncol. 2021 Aug 20;39(24):2667-2675. doi: 10.1200/JCO.20.02822.

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

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