Last Review Date: 12/01/2020

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, 6/2020, 09/2020, 12/2020

I. Length of Authorization 

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

• Use for neo-adjuvant and adjuvant breast cancer is limited to a total of 1 year of treatment [18 cycles] (*Note: When used for metastatic breast cancer, therapy may be continued until disease progression or unmanageable toxicity.)

II. Dosing Limits

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

Perjeta 420 mg/14mL solution for injection:

• Loading Dose: 2 vials
• Maintenance Doses: 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

III. Initial Approval Criteria 

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 used in combination with pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo); AND

Breast Cancer † 

• Used as adjuvant treatment; AND
  • Patient has locally advanced or node positive disease OR early stage disease at high risk of recurrence; AND
  • Used in combination with a trastuzumab-based regimen; OR
• Used as neoadjuvant treatment for breast preservation; AND
  • Patient has locally advanced, inflammatory, or early stage disease; AND
  • Used in combination with trastuzumab and chemotherapy; OR
• Used for recurrent or metastatic disease; AND
  • • • •  
  • Used as first-line therapy in combination with trastuzumab and either paclitaxel OR docetaxel; OR
  • Used as second-line therapy in combination with a trastuzumab-based regimen ‡; AND

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

Colorectal Cancer ‡ 

• Used for RAS and BRAF wild-type (WT) disease in combination with trastuzumab in patients who have not previously received HER2-targeted therapy; AND
  • Used as subsequent therapy for progression of advanced or metastatic disease after at least one prior line of treatment in the advanced or metastatic disease setting; OR
  • Patient is not appropriate for intensive therapy; AND
    • Used as initial systemic therapy for locally unresectable (or medically inoperable) or metastatic disease; OR
    • Used for unresectable or metastatic disease that remains unresectable after primary treatment; OR
    • Used for metastatic disease in patients who have received adjuvant FOLFOX or CapeOX more than 12 months ago OR who have received previous fluorouracil/leucovorin (5-FU/LV) or capecitabine therapy

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

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

IV. Renewal Criteria 

Coverage can be renewed based upon the following criteria:

• Patient continues to meet 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) is >45% OR LVEF is ≥40% and absolute decrease is <10% from baseline (LVEF results must be within the previous 3 months); AND

• Use for neoadjuvant and adjuvant breast cancer treatment is limited to a total of 1 year of treatment (total of 18 cycles)

V. Dosage/Administration 

VI. 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

VII. References

1. Perjeta [package insert]. South San Francisco, CA; Genentech, Inc.; January 2020. Accessed October 2020.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) pertuzumab. National Comprehensive Cancer Network, 2020. 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 October 2020.
3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer 6.2020. National Comprehensive Cancer Network, 2020. 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 October 2020.
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 4.2020. National Comprehensive Cancer Network, 2020. 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 October 2020.
11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Rectal Cancer 6.2020. National Comprehensive Cancer Network, 2020. 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 October 2020.
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. Palmetto GBA, LLC. Local Coverage Article: Billing and Coding: Chemotherapy (A56141). Centers for Medicare and Medicaid Services, Inc. Updated on 05/26/2020 with effective date 04/30/2020. Accessed October 2020.

Appendix 1 – Covered Diagnosis Codes

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

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 Determination (NCD), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

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

.