Last Review Date: 09/05/2024

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, 03/2021, 06/2021, 09/2021, 12/2021, 02/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024, 06/2024, 09/2024

1. Length of Authorization ^1-6,8

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

• Neoadjuvant/preoperative and adjuvant treatment in Breast Cancer may be authorized up to a maximum of fifty-two (52) weeks of treatment.

2. Dosing Limits

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

• 150 mg single-dose vial: 6 vials day 1, then 5 vials every 21 days thereafter
• 420 mg multiple-dose vial: 3 vials day 1, then 2 vials every 21 days thereafter

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

• Herceptin, Hercessi (150 mg SDV):

• Gastric, Esophageal, and Esophagogastric Junction Cancer:
  • Load: 90 billable units x 1 dose
  • Maintenance: 75 billable units every 14 days

• CNS Cancer: 300 billable units every 28 days
• Breast Cancer, Colorectal Cancer & Appendiceal Adenocarcinoma, All other indications: 90 billable units every 21 days

• Ogivri, Kanjinti, Trazimera, Herzuma, Ontruzant (420 mg MDV):

• Gastric, Esophageal, and Esophagogastric Junction Cancer:
  • Load: 92 billable units x 1 dose
  • Maintenance: 69 billable units every 14 days

• CNS Cancer: 276 billable units every 28 days
• Breast Cancer, Colorectal Cancer & Appendiceal Adenocarcinoma, All other indications: 92 billable units every 21 days

3. Initial Approval Criteria ^1-7

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ^1-7

• 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
• Females of reproductive potential have a negative pregnancy test prior to initiating treatment and will use effective contraception during treatment and for 7 months after the last dose; 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 trastuzumab and hyaluronidase-oysk (Herceptin Hylecta) or pertuzumab/trastuzumab and hyaluronidase-zzxf (Phesgo); AND

Breast Cancer † ‡ ^{1-9,11-17,36-39,44-45}

• Used as adjuvant therapy; AND
  • Patient has locally advanced, node positive, or inflammatory disease; AND
    • Used in combination with a taxane-based regimen (e.g., docetaxel, paclitaxel, etc.) with or without pertuzumab; OR
    • Used as a single agent; OR
    • Used in combination with pertuzumab; OR
• Used as neoadjuvant or preoperative therapy; AND
  • Patient has locally advanced, node positive, or inflammatory disease; AND
  • Used in combination with a taxane-based regimen (e.g., docetaxel, paclitaxel, etc.) with or without pertuzumab; OR
• Used for recurrent unresectable (local or regional) or metastatic disease OR inflammatory breast cancer; AND
  • Used as a single agent in patients who have received one or more prior chemotherapy regimens for metastatic disease †; OR
  • Used in combination with one of the following:
    • Paclitaxel as first-line therapy for metastatic disease †
    • Endocrine therapy (e.g., tamoxifen, fulvestrant, or aromatase inhibition with or without lapatinib) in patients with hormone receptor-positive disease; AND
      • Patient is postmenopausal; OR
      • Patient is premenopausal and is treated with ovarian ablation/suppression; OR
      • Patient is premenopausal and will not receive ovarian ablation/suppression (with tamoxifen ONLY); OR
      • Patient is a male (sex assigned at birth) ¥
    • Pertuzumab and a taxane (e.g., docetaxel, paclitaxel) as first-line therapy
    • Capecitabine and tucatinib as second-line therapy and beyond
    • Cytotoxic chemotherapy as fourth-line therapy and beyond
    • Lapatinib (without cytotoxic therapy) as fourth-line therapy and beyond
    • Pertuzumab with or without cytotoxic therapy as subsequent therapy in patients previously treated with chemotherapy and trastuzumab (without pertuzumab)

¥ When an aromatase inhibitor is used in males, suppression of testicular steroidogenesis with a GnRH analog is required.

Central Nervous System (CNS) Cancers ‡ ^8,19,30-31

• Patient has leptomeningeal metastases from breast cancer; AND
  • Trastuzumab will be administered intrathecally; AND
    • Used as primary treatment in patients with good risk status (i.e., KPS ≥60, no major neurologic deficits, minimal systemic disease, or reasonable systemic treatment options); OR
    • Used as maintenance therapy; OR
• Patient has brain metastases from breast cancer; AND
  • Used in combination with one of the following:
    • Pertuzumab
    • Capecitabine and tucatinib in patients previously treated with at least one anti-HER2-based regimen; AND
  • Used in one of the following treatment settings:
    • Used as initial treatment in patients with small asymptomatic brain metastases
    • Patient has recurrent limited brain metastases
    • Patient has recurrent extensive brain metastases with stable systemic disease or reasonable systemic treatment options

• • Patient has relapsed limited brain metastases with either stable systemic disease or reasonable systemic treatment options

Gastric, Esophageal, and Esophagogastric Junction Cancers † ‡ Ф ^{1-8,18,33,34,51}

• Patient has adenocarcinoma; AND
  • Used as induction systemic therapy for relieving dysphagia (applies to Esophageal and Esophagogastric Junction Cancers ONLY ); AND
    • Patient is medically fit and planned for esophagectomy with cT2, N0 (high-risk lesions: lymphovascular invasion, ≥ 3 cm, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, Any N disease; AND
      • Used in combination with chemotherapy; OR

• Used in combination with pembrolizumab, fluoropyrimidine- and platinum-containing chemotherapy; AND
  • Tumor expresses PD-L1 (CPS ≥ 1) as determined by an FDA-approved or CLIA compliant testv
• Patient has early-stage disease* with favorable histology (applies to Gastric Cancer ONLY); AND
  • Patient has completed an endoscopic resection; AND
    • Used in combination with chemotherapy; OR
    • Used in combination with pembrolizumab, fluoropyrimidine- and platinum-containing chemotherapy; AND

• • Tumor expresses PD-L1 (CPS ≥ 1) as determined by an FDA-approved or CLIA compliant testv; OR
• Patient is not a surgical candidate or has unresectable locally advanced, recurrent, or metastatic disease; AND
  • Used as first-line therapy; AND

• • Used in combination with chemotherapy; OR
  • Used in combination with pembrolizumab, fluoropyrimidine- and platinum-containing chemotherapy; AND
    • Tumor expresses PD-L1 (CPS ≥ 1) as determined by an FDA-approved or CLIA compliant testv

* Endoscopic features suggestive of deep submucosal invasion include converging folds, irregular surface pattern, and ulceration in a large gastric mass

Endometrial Carcinoma – Uterine Neoplasms ‡ ^8,20,35

• Used in combination with carboplatin and paclitaxel, followed by single agent maintenance therapy; AND
• Patient has uterine serous carcinoma OR carcinosarcoma; AND
  • Patient has stage III/IV disease; OR
  • Patient has recurrent disease and has not received prior trastuzumab therapy; AND

• Used as first-line therapy; AND

• Patient does not have isolated metastases; OR

• Used as subsequent therapy

Colorectal Cancer (CRC) ‡ ^8,10,32

• Patient has RAS and BRAF wild-type (WT) disease; AND
• Used in combination with pertuzumab, lapatinib, or tucatinib; 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-directed therapy; AND
      • 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 locally 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-directed therapy; AND
    • 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 ‡ ^8,10

• Patient has RAS and BRAF wild-type (WT) disease; AND
• Used in combination with pertuzumab, lapatinib, or tucatinib; 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 ‡ ^8,40-43

• Patient has salivary gland tumors; AND
• Used as a single agent OR in combination with either docetaxel or pertuzumab; AND
• Patient has recurrent disease with one of the following:
  • 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) ‡ ^8,46,47,52

• 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 either pertuzumab or tucatinib

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 ^1-7

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: cardiomyopathy (e.g., left ventricular cardiac dysfunction, arrhythmias, cardiac failure, etc.), pulmonary toxicity (e.g., dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, etc.), severe or febrile neutropenia, severe infusion-related reactions, etc.; AND
• Left ventricular ejection fraction (LVEF) obtained 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 (neoadjuvant/preoperative and adjuvant therapy) ^1-8

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

5. Dosage/Administration ^{1-9,19,20,30,32-34,41-43,46,50,52-53}

6. Billing Code/Availability Information

7. References

1. Herceptin [package insert]. South San Francisco, CA; Genentech, Inc.; June 2024.  Accessed July 2024.
2. Ogivri [package insert]. Cambridge, MA; Biocon Biologics, Inc.; July 2023. Accessed July 2024.
3. Kanjinti [package insert]. Thousand Oaks, CA; Amgen, Inc.; October 2022. Accessed July 2024.
4. Trazimera [package insert]. Cork, Ireland; Pfizer Ireland Pharmaceuticals; November 2020. Accessed July 2024.
5. Herzuma [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Celltrion, Inc.; May 2019. Accessed July 2024.
6. Ontruzant [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Samsung Bioepsis Co., Ltd.; June 2021. Accessed July 2024.
7. Hercessi [package insert]. Shanghai, China; Accord BioPharma Inc.; April 2024. Accessed July 2024.
8. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for trastuzumab. 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 July 2024.
9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer, Version 4.2024. 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 July 2024.
10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Colon Cancer, Version 4.2024. 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 July 2024.
11. 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.
12. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673-1684 and supplementary appendix.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from https://www.hoparx.org/about-us/advocacy-awareness/issue-briefs/
24. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Central Nervous System Cancers, 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 July 2024.
32. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Rectal Cancer, Version 3.2024. 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 July 2024.
33. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Gastric Cancer, Version 3.2024. 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 August 2024.
34. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Esophageal and Esophagogastric Junction Cancers, Version 4.2024. 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 August 2024.
35. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Uterine Neoplasms, 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 July 2024.
36. 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.
37. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273-1283.
38. 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.
39. 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.
40. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Head and Neck Cancers, Version 4.2024. 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 July 2024.
41. Thorpe L, Schrock A, Erlich R, et al. Significant and durable clinical benefit from trastuzumab in 2 patients with HER2-amplified salivary gland cancer and a review of the literature. Head Neck 2017 Mar;39(3):E40-E44. doi: 10.1002/hed.24634. Epub 2016 Dec 22.
42. Kurzrock R, Bowles D, Kang H, et al. Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study. Annals of Oncology, Volume 31, Issue 3, 412 – 421
43. Takahashi H, Tada Y, Saotome T, et al. Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Positive Salivary Duct Carcinoma. J Clin Oncol 2019 Jan 10;37(2):125-134. doi: 10.1200/JCO.18.00545. Epub 2018 Nov 19.
44. Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. J Clin Oncol. 2021 May 1;39(13):1485-1505. doi: 10.1200/JCO.20.03399. Epub 2021 Jan 28. PMID: 33507815; PMCID: PMC8274745.
45. 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.
46. 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.
47. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Biliary Tract Cancers, Version 3.2024. 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 July 2024.
48. Buza N, English DP, Santin AD, Hui P. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice. Mod Pathol. 2013 Dec;26(12):1605-12. doi: 10.1038/modpathol.2013.113.
49. Bartley AN, Washington MK, Colasacco C, et al. HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017 Feb;35(4):446-464. doi: 10.1200/JCO.2016.69.4836.
50. 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.
51. Janjigian YY, Kawazoe A, Bai Y, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet 2023;402:2197-2208.
52. Nakamura Y, Mizuno N, Sunakawa Y, et al. Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. J Clin Oncol. 2023 Dec 20;41(36):5569-5578. doi: 10.1200/JCO.23.00606. Epub 2023 Sep 26.
53. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Intrathecal Trastuzumab: Central Nervous System Cancers Chemotherapy Order Template, CNS30. 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 August 2024.
54. 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 July 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.