vp-0057
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Trastuzumab: Herceptin®; Ogivri™; Kanjinti™; Trazimera™; Herzuma™; Ontruzant™ (Intravenous)

Policy Number: VP-0057

Last Review Date: 06/06/2022

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

FOR PEEHIP Members Only -Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

I. Length of Authorization 1

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 fifty-two (52) weeks of treatment [18 cycles].

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

Indication

Load

(1-time)

Load Billable Units

(1-time)

Maint.

Maint. Billable Units

Interval (Days)

Herceptin (150 mg SDV)

Breast Cancer, Colorectal Cancer, Appendiceal Adenocarcinoma

4 mg/kg

45

2 mg/kg

30

7

8 mg/kg

90

6 mg/kg

75

21

Gastric, Esophageal, GEJ Cancer

6 mg/kg

75

4 mg/kg

45

14

8 mg/kg

90

6 mg/kg

75

21

CNS mets from Breast Cancer, Uterine Cancer, Head and Neck Cancer, Hepatobiliary Cancers

8 mg/kg

90

6 mg/kg

75

21

Leptomeningeal Metastases from Breast Cancer

N/A

N/A

100 mg

15

7

 

Indication

Load

(1-time)

Load Billable Units

(1-time)

Maint.

Maint. Billable Units

Interval (Days)

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

Breast Cancer, Colorectal Cancer; Appendiceal Adenocarcinoma

4 mg/kg

46

2 mg/kg

23

7

8 mg/kg

92

6 mg/kg

69

21

Gastric, Esophageal, GEJ Cancer

6 mg/kg

69

4 mg/kg

46

14

8 mg/kg

92

6 mg/kg

69

21

CNS mets from Breast Cancer, Uterine Cancer, Head and Neck Cancer, Hepatobiliary Cancers

8 mg/kg

92

6 mg/kg

69

21

Leptomeningeal Metastases from Breast Cancer

N/A

N/A

100 mg

10

7

III. Initial Approval Criteria 1

Coverage is provided in the following conditions:

  • Trazimera (trastuzumab-qyyp) and Kanjinti (trastuzumab-anns) are the preferred products. Patient must have tried and had an inadequate response or intolerance to, or a contraindication to Trazimera and Kanjinti, attributable to the biosimilar formulation, prior to consideration of a non-preferred trastuzumab product including Herceptin (trastuzumab), Ogivri (trastuzumab-dkst), Herzuma (trastuzumab-pkrb), and Ontruzant (trastuzumab-dttb) OR Patient is continuing treatment with a non-preferred trastuzumab product including Herceptin, Ogivri, Herzuma or Ontruzant; AND

  • 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 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 † ‡ 1-8,10-16,35-38,43,44

  • 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, node positive, or inflammatory disease; 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 or metastatic disease OR inflammatory breast cancer with no response to preoperative systemic therapy; AND
    • Used as a single agent in patients who have received one or more prior chemotherapy regimens 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:
      • Pertuzumab and a taxane (e.g., docetaxel, paclitaxel) as first-line therapy
      • Capecitabine and tucatinib as second-line therapy and beyond
      • Cytotoxic chemotherapy as third-line therapy and beyond
      • Lapatinib (without cytotoxic therapy) as third-line therapy and beyond
      • Pertuzumab with or without cytotoxic therapy as subsequent therapy in patients previously treated with chemotherapy and trastuzumab (without pertuzumab)

Central Nervous System Cancer ‡ 7,18,29,30

  • Patient has leptomeningeal metastases from breast cancer; AND
    • Trastuzumab will be administered intrathecally; OR
  • Patient has brain metastases from breast cancer; AND
    • Used in combination with capecitabine and tucatinib; AND
    • Patient has previously been treated with at least one HER2-directed regimen; AND
      • Used as initial treatment in patients with small asymptomatic brain metastases; OR
      • Patient has recurrent limited brain metastases; OR
      • Patient has recurrent extensive brain metastases with stable systemic disease or reasonable systemic treatment options; OR
      • Patient has relapsed limited brain metastases with either stable systemic disease or reasonable systemic treatment options

Gastric, Esophageal, and Esophagogastric Junction Cancers † Ф 1-7,17,32,33

  • Patient has unresectable (or medically inoperable) locally advanced, recurrent, or metastatic adenocarcinoma; AND
  • Used as first-line therapy in combination with chemotherapy with or without pembrolizumab (excluding use with anthracyclines or in combination with DCF [docetaxel, carboplatin, and fluorouracil])

Uterine Cancer (Endometrial Carcinoma) ‡ 7,19,34

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

Colorectal Cancer ‡ 7,9,31

  • Patient has RAS and BRAF wild-type (WT) disease; AND
  • Used in combination with pertuzumab or lapatinib; AND
  • Patient has not previously received HER2-directed 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
    • Used as primary treatment for unresectable (or medically inoperable), locally advanced, or metastatic disease; AND
      • Patient is not appropriate for intensive therapy

Appendiceal Adenocarcinoma – Colorectal Cancer ‡ 7,9

  • Patient has advanced or metastatic disease; AND
  • Patient has RAS and BRAF wild-type (WT) disease; AND
  • Used in combination with pertuzumab or lapatinib; AND
  • Patient has not previously received HER2-targeted therapy; AND
    • Used as initial therapy if intensive therapy is not recommended; OR
    • Used as subsequent therapy

Head and Neck Cancer ‡ 7,39-42

  • Patient has salivary gland tumors; AND
  • Used as a single agent OR in combination with either docetaxel or pertuzumab; AND
  • Used for one of the following:
    • Recurrent disease with distant metastases
    • Unresectable locoregional recurrence with prior radiation therapy (RT)
    • Recurrent unresectable second primary with prior RT

Hepatobiliary Cancers ‡ 7,45,46

  • Patient has gallbladder cancer, extrahepatic cholangiocarcinoma, or intrahepatic cholangiocarcinoma; AND
  • Used as subsequent treatment for progression on or after systemic treatment for unresectable or metastatic disease; AND
  • Used in combination with pertuzumab

*HER2-positive overexpression criteria

Breast, CNS, Uterine, Head and Neck, and Hepatobiliary Cancer: 8,10

  • Immunohistochemistry (IHC) assay 3+; OR
  • Dual-probe in situ hybridization (ISH) assay HER2/CEP17 ratio2.0 AND average HER2 copy number 4.0 signals/cell; OR
  • Dual-probe in situ hybridization (ISH) assay AND concurrent IHC indicating one of the following:
          • HER2/CEP17 ratio 2.0 AND average HER2 copy number < 4.0 signals/cell AND concurrent IHC 3+; OR
          • HER2/CEP17 ratio < 2.0 AND average HER2 copy number 6.0 signals/cell AND concurrent IHC 2+ or 3+; OR
    • HER2/CEP17 ratio < 2.0 AND average HER2 copy number ≥ 4.0 and < 6.0 signals/cell AND concurrent IHC 3+

Gastric, Esophageal, and Esophagogastric Junction Cancer: 32,33,48

  • Immunohistochemistry (IHC) assay 3+; OR
  • Fluorescence in situ hybridization (FISH) or in situ hybridization (ISH) assay AND concurrent IHC indicating one of the following:
          • HER2/CEP17 ratio ≥ 2.0 AND concurrent IHC 2+; OR
          • Average HER2 copy number ≥ 6.0 signals/cell AND concurrent IHC 2+

Colorectal Cancer and Appendiceal Adenocarcinoma: 9,31

  • Immunohistochemistry (IHC) assay 3+; OR
  • Fluorescence in situ hybridization (FISH) HER2/CEP17 ratio ≥ 2 AND concurrent IHC 2+; OR
  • Next-generation sequencing (NGS) panel HER2 amplification

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 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: cardiotoxicity (e.g., left ventricular dysfunction, cardiomyopathy, etc.), pulmonary toxicity (e.g., dyspnea, interstitial pneumonitis, etc.), severe or febrile neutropenia, 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 and adjuvant therapy)

  • Patient has not exceeded a maximum of fifty-two (52) weeks of treatment (total 18 cycles)

V. Dosage/Administration 1-9,18,19,29,31-33,40-42,45

Indication

Dose

Breast Cancer

Neoadjuvant/Adjuvant Therapy

Combination Therapy

  • Administer an initial dose of 4 mg/kg intravenously followed by 2 mg/kg intravenously weekly during chemotherapy for up to 18 weeks.
  • One week following the last weekly dose of trastuzumab, administer 6 mg/kg intravenously every three weeks.

OR

  • Administer an initial dose of 4 mg/kg intravenously followed by 2 mg/kg intravenously weekly.

OR

  • Administer an initial dose at 8 mg/kg intravenously followed by 6 mg/kg intravenously every three weeks.

Single-Agent Therapy (following chemotherapy)

  • Administer an initial dose at 8 mg/kg intravenously, followed by subsequent doses at 6 mg/kg intravenously every three weeks.

Note: Use for neoadjuvant and adjuvant treatment is limited to a total of 52 weeks of treatment (total of 18 cycles).

Recurrent or Metastatic Disease (alone or in combination with chemotherapy)

Loading dose: 4 mg/kg intravenously x 1 for every 7-day dosing schedule

Maintenance dose: 2 mg/kg intravenously every 7 days

OR

Loading dose: 8 mg/kg intravenously x 1 for every 21-day dosing schedule

Maintenance dose: 6 mg/kg every 21 days

Note: Treat until disease progression or intolerable toxicity.

Gastric, Esophageal, and Esophagogastric Junction Cancers

Loading dose: 8 mg/kg intravenously x 1 for every 21-day dosing schedule

Maintenance dose: 6 mg/kg intravenously every 21 days

OR

Loading dose: 6 mg/kg intravenously x 1 for every 14-day dosing schedule

Maintenance dose: 4 mg/kg intravenously every 14 days

Note: Treat until disease progression or intolerable toxicity.

Colorectal Cancer & Appendiceal Adenocarcinoma

Loading dose: 8 mg/kg intravenously x 1 for every 21-day dosing schedule

Maintenance dose: 6 mg/kg intravenously every 21 days

OR

Loading dose: 4 mg/kg intravenously x 1 for every 7-day dosing schedule

Maintenance dose: 2 mg/kg intravenously every 7 days

Note: Treat until disease progression or intolerable toxicity.

Leptomeningeal Metastases from Breast Cancer

Escalating doses up to 100 mg intrathecally weekly*

*Dosing is highly variable and should be individualized.

Note: Treat until disease progression or intolerable toxicity.

All other indications

Loading dose: 8 mg/kg intravenously x 1 for every 21-day dosing schedule

Maintenance dose: 6 mg/kg intravenously every 21 days

Note: Treat until disease progression or intolerable toxicity.

VI. Billing Code/Availability Information

Brand Name

HCPCS

HCPCS Description

1 BU

Vial Size & Type

NDCs

Herceptin

J9355

Injection, trastuzumab, excludes biosimilar, 10 mg

10 mg

150 mg SDV

50242-0132-xx

420 mg MDV (discontinued)

50242-0333-xx (discontinued)

Ogivri

Q5114

Injection, Trastuzumab-dkst, biosimilar, (Ogivri), 10 mg

10 mg

150 mg SDV

67457-0991-xx

420 mg MDV (with diluent)

67457-0847-xx

420 mg MDV (no diluent)

67457-0845-xx

Kanjinti

Q5117

Injection, trastuzumab-anns, biosimilar, (Kanjinti), 10 mg

10 mg

150 mg SDV

55513-0141-xx

420 mg MDV

55513-0132-xx

Trazimera

Q5116

Injection, trastuzumab-qyyp, biosimilar, (Trazimera), 10 mg

10 mg

150 mg SDV

00069-0308-xx

420 mg MDV

00069-0305-xx

Herzuma

Q5113

Injection, Trastuzumab-pkrb, biosimilar, (Herzuma), 10 mg

10 mg

150 mg SDV

63459-0303-xx

420 mg MDV

63459-0305-xx

Ontruzant

Q5112

Injection, Trastuzumab-dttb, biosimilar, (Ontruzant), 10 mg

10 mg

150 mg SDV

78206-0147-xx

420 mg MDV

78206-0148-xx

Notes:

  • Herceptin is only available as a single-dose vial; therefore, the JW modifier is allowed
  • Ogivri, Kanjinti, Trazimera, Herzuma, & Ontruzant are available as both single-dose and multi-dose vials. Approvals are based upon use of the MDV; therefore, the JW modifier is not allowed

VII. References

  1. Herceptin [package insert]. South San Francisco, CA; Genentech, Inc.; February 2021.  Accessed April 2022.
  2. Ogivri [package insert]. Morgantown, WV; Mylan Pharmaceuticals, Inc.; February 2021. Accessed April 2022.
  3. Kanjinti [package insert]. Thousand Oaks, CA; Amgen, Inc.; October 2019. Accessed April 2022.
  4. Trazimera [package insert]. Cork, Ireland; Pfizer Ireland Pharmaceuticals; November 2020. Accessed April 2022.
  5. Herzuma [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Celltrion, Inc.; May 2019. Accessed April 2022.
  6. Ontruzant [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Samsung Bioepsis Co., Ltd.; June 2021. Accessed April 2022.
  7. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Trastuzumab. National Comprehensive Cancer Network, 2022. 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 2022.
  8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer 3.2022. National Comprehensive Cancer Network, 2022. 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 2022.
  9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer 1.2022. National Comprehensive Cancer Network, 2022. 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 April 2022.
  10. 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.
  11. 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.
  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.
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  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.
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  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.
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  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 2.2021. National Comprehensive Cancer Network, 2022. 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 April 2022.
  31. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer 1.2022. National Comprehensive Cancer Network, 2022. 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 April 2022.
  32. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer 2.2022. National Comprehensive Cancer Network, 2022. 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 April 2022.
  33. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers 2.2022. National Comprehensive Cancer Network, 2022. 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 2022.
  34. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms 1.2022. National Comprehensive Cancer Network, 2022. 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 April 2022.
  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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  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. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers 2.2022. National Comprehensive Cancer Network, 2022. 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 2022.
  40. 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.
  41. 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
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  44. 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.
  45. 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.
  46. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers, Version 1.2022. National Comprehensive Cancer Network, 2022. 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 April 2022.
  47. 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.
  48. 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.
  49. 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 April 2022.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

C06.9

Malignant neoplasm of mouth, unspecified

C07

Malignant neoplasm of parotid gland

C08.0

Malignant neoplasm of submandibular gland

C08.1

Malignant neoplasm of sublingual gland

C08.9

Malignant neoplasm of major salivary gland, unspecified

C15.3

Malignant neoplasm of upper third of esophagus

C15.4

Malignant neoplasm of middle third of esophagus

C15.5

Malignant neoplasm of the lower third of esophagus

C15.8

Malignant neoplasm of overlapping sites of esophagus

C15.9

Malignant neoplasm of esophagus, unspecified

C16.0

Malignant neoplasm of cardia

C16.1

Malignant neoplasm of fundus of stomach

C16.2

Malignant neoplasm of body of stomach

C16.3

Malignant neoplasm of pyloric antrum

C16.4

Malignant neoplasm of pylorus

C16.5

Malignant neoplasm of lesser curvature of stomach, unspecified

C16.6

Malignant neoplasm of greater curvature of stomach, unspecified

C16.8

Malignant neoplasm of overlapping sites of stomach

C16.9

Malignant neoplasm of stomach, unspecified

C18.0

Malignant neoplasm of cecum

C18.1

Malignant neoplasm of appendix

C18.2

Malignant neoplasm of ascending colon

C18.3

Malignant neoplasm of hepatic flexure

C18.4

Malignant neoplasm of transverse colon

C18.5

Malignant neoplasm of splenic flexure

C18.6

Malignant neoplasm of descending colon

C18.7

Malignant neoplasm of sigmoid colon

C18.8

Malignant neoplasm of overlapping sites of large intestines

C18.9

Malignant neoplasm of colon, unspecified

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.8

Malignant neoplasm of overlapping sites of rectum, anus and anal canal

C22.1

Intrahepatic bile duct carcinoma

C23

Malignant neoplasm of gallbladder

C24.0

Malignant neoplasm of extrahepatic bile duct

C24.8

Malignant neoplasm of overlapping sites of biliary tract

C24.9

Malignant neoplasm of biliary tract, unspecified

C50.011

Malignant neoplasm of nipple and areola, right female breast

C50.012

Malignant neoplasm of nipple and areola, left female breast

C50.019

Malignant neoplasm of nipple and areola, unspecified female breast

C50.021

Malignant neoplasm of nipple and areola, right female breast

C50.022

Malignant neoplasm of nipple and areola, left female breast

C50.029

Malignant neoplasm of nipple and areola, unspecified female breast

C50.111

Malignant neoplasm of central portion of right female breast

C50.112

Malignant neoplasm of central portion of left female breast

C50.119

Malignant neoplasm of central portion of unspecified female breast

C50.121

Malignant neoplasm of central portion of right male breast

C50.122

Malignant neoplasm of central portion of left male breast

C50.129

Malignant neoplasm of central portion of unspecified male breast

C50.211

Malignant neoplasm of upper-inner quadrant of right female breast

C50.212

Malignant neoplasm of upper-inner quadrant of left female breast

C50.219

Malignant neoplasm of upper-inner quadrant of unspecified female breast

C50.221

Malignant neoplasm of upper-inner quadrant of right male breast

C50.222

Malignant neoplasm of upper-inner quadrant of left male breast

C50.229

Malignant neoplasm of upper-inner quadrant of unspecified male breast

C50.311

Malignant neoplasm of lower-inner quadrant of right female breast

C50.312

Malignant neoplasm of lower-inner quadrant of left female breast

C50.319

Malignant neoplasm of lower-inner quadrant of unspecified female breast

C50.321

Malignant neoplasm of lower-inner quadrant of right male breast

C50.322

Malignant neoplasm of lower-inner quadrant of left male breast

C50.329

Malignant neoplasm of lower-inner quadrant of unspecified male breast

C50.411

Malignant neoplasm of upper-outer quadrant of right female breast

C50.412

Malignant neoplasm of upper-outer quadrant of left female breast

C50.419

Malignant neoplasm of upper-outer quadrant of unspecified female breast

C50.421

Malignant neoplasm of upper-outer quadrant of right male breast

C50.422

Malignant neoplasm of upper-outer quadrant of left male breast

C50.429

Malignant neoplasm of upper-outer quadrant of unspecified male breast

C50.511

Malignant neoplasm of lower-outer quadrant of right female breast

C50.512

Malignant neoplasm of lower-outer quadrant of left female breast

C50.519

Malignant neoplasm of lower-outer quadrant of unspecified female breast

C50.521

Malignant neoplasm of lower-outer quadrant of right male breast

C50.522

Malignant neoplasm of lower-outer quadrant of left male breast

C50.529

Malignant neoplasm of lower-outer quadrant of unspecified male breast

C50.611

Malignant neoplasm of axillary tail of right female breast

C50.612

Malignant neoplasm of axillary tail of left female breast

C50.619

Malignant neoplasm of axillary tail of unspecified female breast

C50.621

Malignant neoplasm of axillary tail of right male breast

C50.622

Malignant neoplasm of axillary tail of left male breast

C50.629

Malignant neoplasm of axillary tail of unspecified male breast

C50.811

Malignant neoplasm of overlapping sites of right female breast

C50.812

Malignant neoplasm of overlapping sites of left female breast

C50.819

Malignant neoplasm of overlapping sites of unspecified female breast

C50.821

Malignant neoplasm of overlapping sites of right male breast

C50.822

Malignant neoplasm of overlapping sites of left male breast

C50.829

Malignant neoplasm of overlapping sites of unspecified male breast

C50.911

Malignant neoplasm of unspecified site of right female breast

C50.912

Malignant neoplasm of unspecified site of left female breast

C50.919

Malignant neoplasm of unspecified site of unspecified female breast

C50.921

Malignant neoplasm of unspecified site of right male breast

C50.922

Malignant neoplasm of unspecified site of left male breast

C50.929

Malignant neoplasm of unspecified site of unspecified male breast

C54.0

Malignant neoplasm of isthmus uteri

C54.1

Malignant neoplasm of endometrium

C54.2

Malignant neoplasm of myometrium

C54.3

Malignant neoplasm of fundus uteri

C54.8

Malignant neoplasm of overlapping sites of corpus uteri

C54.9

Malignant neoplasm of corpus uteri, unspecified

C55

Malignant neoplasm of uterus, part unspecified

C78.00

Secondary malignant neoplasm of unspecified lung

C78.01

Secondary malignant neoplasm of right lung

C78.02

Secondary malignant neoplasm of left lung

C78.6        

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

C79.31

Secondary malignant neoplasm of brain

C79.32

Secondary malignant neoplasm of cerebral meninges

D37.1

Neoplasm of uncertain behavior of stomach

D37.8

Neoplasm of uncertain behavior of other specified digestive organs

D37.9

Neoplasm of uncertain behavior of digestive organ, unspecified

Z85.00

Personal history of malignant neoplasm of unspecified digestive organ

Z85.01

Personal history of malignant neoplasm of esophagus

Z85.028

Personal history of other malignant neoplasm of stomach

Z85.038

Personal history of other malignant neoplasm of large intestine

Z85.3

Personal history of malignant neoplasm of breast

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: https://www.cms.gov/medicare-coverage-database/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):  

Jurisdiction(s): N(9)

NCD/LCD Document (s): A56660

https://www.cms.gov/medicare-coverage-database/new-search/search-results.aspx?keyword=a56660&areaId=all&docType=NCA%2CCAL%2CNCD%2CMEDCAC%2CTA%2CMCD%2C6%2C3%2C5%2C1%2CF%2CP

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA,HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC