Last Review Date: 12/01/2020

Date of Origin: 10/17/2008

Dates Reviewed: 06/2009, 12/2009, 03/2010,  09/2010, 03/2011, 06/2011, 09/2011, 12/2011, 03/2012, 06/2012, 09/2012, 11/2012, 12/2012, 03/2013, 06/2013, 09/2013, 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

I. Length of Authorization 

Coverage is provided for six months and may be renewed.

• Use in the neo-adjuvant and adjuvant setting is limited to a total of 52 weeks of treatment.

II. Dosing Limits

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

• Herceptin 150 mg single-dose vial: 7 vials every 21 days
• Herceptin 420 mg multiple-dose vial: 3 vials every 21 days
• Ogivri 150 mg single-dose vial: 7 vials every 21 days
• Ogivri 420 mg multiple-dose vial: 3 vials every 21 days
• Kanjinti 150 mg single-dose vial: 7 vials every 21 days
• Kanjinti 420 mg multiple-dose vial:  3 vials every 21 days
• Trazimera 420 mg multiple-dose vial:  3 vials every 21 days
• Herzuma 150 mg single-dose vial: 7 vials every 21 days
• Herzuma 420 mg multiple-dose vial: 3 vials every 21 days
• Ontruzant 150 mg single-dose vial: 7 vials every 21 days
• Ontruzant 420 mg multiple-dose vial: 3 vials every 21 days

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

Breast Cancer & Colorectal Cancer

Gastric/Esophageal/Gastro-esophageal Junction Cancers

CNS Cancer (Leptomeningeal metastases from breast cancer)

• 15 billable units every 7 days

CNS Cancer (Limited/Extensive brain metastases) & Uterine Cancer

• 90 billable units, followed by 75 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 substituted with or for ado-trastuzumab emtansine (Kadcyla) or fam-trastuzumab deruxtecan-nxki (Enhertu); AND
• Will not be used in combination with trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) or pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo); AND

Breast Cancer † 

• Used as adjuvant therapy; AND
  • Used in combination with a taxane-based regimen (e.g., docetaxel, paclitaxel, etc.) †; OR
  • Used as a single agent following chemotherapy; OR
  • Used in combination with pertuzumab for locally advanced or node positive disease; OR
• Used as neoadjuvant or preoperative therapy for locally advanced disease or node positive disease; AND
  • Used in combination with a taxane-based regimen (e.g., docetaxel, paclitaxel, etc.) with or without pertuzumab; OR
• Used for recurrent or metastatic disease; AND
  • Used as a single agent in patients who have received one or more prior treatments for metastatic disease †; OR
  • Used as first-line therapy in combination with paclitaxel †; OR
  • Used in combination with endocrine therapy (e.g., tamoxifen, fulvestrant, or aromatase inhibition with or without lapatinib) in patients with hormone-receptor positive disease; AND
    • Patient is post-menopausal; OR
    • Patient is pre-menopausal and is treated with ovarian ablation/suppression; OR
    • Patient is a male receiving concomitant suppression of testicular steroidogenesis; OR
  • Used in combination with one of the following:
    • cytotoxic chemotherapy
    • lapatinib (without cytotoxic therapy)
    • capecitabine plus tucatinib (includes use in advanced unresectable disease)  in patients who have received one or more lines of prior HER2-targeted therapy in the metastatic setting
    • pertuzumab and a taxane (e.g., docetaxel, paclitaxel) as first-line therapy
    • pertuzumab with or without cytotoxic therapy as one line of therapy beyond first-line therapy in patients who were previously treated with trastuzumab without pertuzumab

Central Nervous System Cancer ‡ 

• Patient has leptomeningeal metastases from breast cancer; AND
  • Trastuzumab will be administered intrathecally; OR
• Patient has limited or extensive brain metastases from breast cancer; AND
  • Used in combination with capecitabine and tucatinib; AND
  • Patient previously received at least one HER2-directed therapy; AND
    • Used as primary treatment in patients with small asymptomatic brain metastases; OR
    • Used for relapsed disease in patients with limited brain metastases who are systemically stable or have other reasonable systemic treatment options; OR
    • Used for recurrent limited brain metastases; OR
    • Used for recurrent disease in patients with extensive brain metastases who are systemically stable or have other reasonable systemic treatment options

Gastric, Esophageal, and Esophagogastric Junction Cancers † Ф 

• Used in combination with chemotherapy (excluding use with anthracyclines or in combination with DCF [docetaxel, carboplatin, and fluorouracil]) as first-line therapy; AND
• Patient has metastatic adenocarcinoma

     Uterine Cancer (Endometrial Carcinoma) ‡ 

• Used in combination with carboplatin and paclitaxel; AND
• Patient has advanced (stage III/IV) or recurrent uterine serous carcinoma

Colorectal Adenocarcinoma ‡ 

• Used in combination with pertuzumab or lapatinib in patients who have not previously received HER2-targeted therapy; AND
• Patient has RAS and BRAF wild-type (WT) disease; 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 the following: cardiotoxicity (e.g., left ventricular dysfunction, cardiomyopathy, etc.), pulmonary toxicity (e.g., dyspnea, interstitial pneumonitis, etc.), neutropenia, infusion-related reactions, etc.; AND
  • LVEF is within the institutional normal limits, but has not had an absolute decrease of  ≥ 16% from pre-treatment baseline (LVEF results must be within the previous 3 months); OR
  • LVEF is below the institutional lower limits of normal, but has not had an absolute decrease of  ≥ 10% from pre-treatment 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 52 weeks of therapy

V. Dosage/Administration 

VI. Billing Code/Availability Information

HCPCS Code:

• J9355 - Injection, trastuzumab, excludes biosimilar, 10 mg; 1 billable unit (bu) = 10 mg
• Q5114 – Injection, Trastuzumab-dkst, biosimilar, (Ogivri), 10 mg; 1 bu = 10 mg
• Q5117 - Injection, trastuzumab-anns, biosimilar, (Kanjinti), 10 mg: 1 bu = 10 mg
• Q5116 − Injection, trastuzumab-qyyp, biosimilar, (Trazimera), 10 mg; 1 bu = 10 mg
• Q5113 − Injection, Trastuzumab-pkrb, biosimilar, (Herzuma), 10 mg; 1 bu = 10 mg
• Q5112 – Injection, Trastuzumab-dttb, biosimilar, (Ontruzant), 10 mg; 1 bu = 10 mg

NDC(s):

• Herceptin 150 mg single-dose vial; powder for injection: 50242-0132-xx
• Herceptin 420 mg multiple-dose vial; powder for injection: 50242-0333-xx*
• Ogivri 150 mg single-dose vial; powder for injection: 67457-0991-xx
• Ogivri 420 mg multiple-dose vial; powder for injection: 67457-0847-xx
• Kanjinti 150 mg single-dose vial powder for injection: 55513-0141-xx
• Kanjinti 420 mg multiple-dose vial; powder for injection: 55513-0132-xx
• Trazimera 420 mg multiple-dose vial; lyophilized powder for injection: 00069-0305-xx
• Herzuma 150 mg single-dose vial; powder for injection: 63459-0303-xx
• Herzuma 420 mg multiple-dose vial: powder for injection: 63459-0305-xx
• Ontruzant 150 mg single-dose vial; powder for injection: 00006-5033-xx
• Ontruzant 420 mg multiple-dose vial; powder for injection: 00006-5034-xx

*Note: Not commercially available

VII. References

1. Herceptin [package insert]. South San Francisco, CA; Genentech, Inc; November 2018.  Accessed October 2020.
2. Ogivri [package insert]. Steinhausen, SZ; Mylan, Inc; June 2020. Accessed October 2020.
3. Kanjinti [package insert]. Thousand Oaks, CA; Amgen, Inc; October 2019. Accessed October 2020.
4. Trazimera [package insert]. Cork, Ireland; Pfizer Ireland, Inc; November 2019. Accessed  October 2020.
5. Herzuma [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Celltrion, Inc; May 2019.  Accessed October 2020.
6. Ontruzant [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Samsung Bioepsis; March 2020. Accessed October 2020.
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8. 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.
9. 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.
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12. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.
13. Cameron D, Piccart-Gebhart MJ, Gelber RD et al. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-1205.
14. Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002 Feb 1;20(3):719-26.
15. Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9.
16. Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer.
17. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. J Clin Oncol. 2006 Jun 20;24(18):2786-92.
18. Zagouri F, Sergentanis TN, Bartsch R, et al. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat 2013; 139:13-22.
19. Fader AN, Roque DM, Siegel E, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol. 2018 Jul 10;36(20):2044-2051. doi: 10.1200/JCO.2017.76.5966. Epub 2018 Mar 27.
20. 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.
21. Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.
22. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf
23. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
24. von Minckwitz G, Colleoni M, Kolberg HC, et al. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018;19:987-998.
25. Rugo HS, Barve A, Waller CF, et al. Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)-positive metastatic breast cancer: a randomized clinical trial. JAMA. 2017;317:37–47.
26. Pivot X, Bondarenko I, Nowecki Z, et al. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018;36:968-974.
27. Pegram MD, Bondarenko I, Zorzetto MMC, et al. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019;120:172-182.
28. Esteva FJ, Baranau YV, Baryash V, et al. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial. Cancer Chemother Pharmacol. 2019 Oct;84(4):839-847.
29. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med.2020;382:597-609.
30. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Central Nervous System Cancers 3.2020. 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 August 2020.
31. 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.
32. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Gastric Cancer 3.2020. 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.
33. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Esophageal and Esophagogastric Junction Cancers 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.
34. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Uterine Neoplasms 1.2021. 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.
35. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32(33):3744-3752.
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37. Eiermann W; International Herceptin Study Group. Trastuzumab combined with chemotherapy for the treatment of HER2-positive metastatic breast cancer: pivotal trial data. Ann Oncol. 2001;12 Suppl 1:S57-S62.
38. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17(9):2639-2648.
39. First Coast Service Options, Inc. Local Coverage Article: Billing and Coding: Trastuzumab -Trastuzumab Biologics (A56660). Centers for Medicare & Medicaid Services, Inc. Updated on 07/22/2020 with effective date of 07/01/2020. Accessed October 2020.
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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 Articles (LCAs) and Local Coverage Determinations (LCDs) 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/LCA/LCD):