BlueCross BlueShield of Tennessee Medical Policy Manual

Trastuzumab Products - Intravenous (Herceptin®, Ontruzant®, Herzuma®, Ogivri®, Trazimera™, Kanjinti™)

NDC CODE(S)

50242-0132-XX HERCEPTIN 150MG Solution Reconstituted (GENENTECH)

00006-5033-XX ONTRUZANT 150MG Solution Reconstituted (MERCK SHARP & D)

00006-5034-XX ONTRUZANT 420MG Solution Reconstituted (MERCK SHARP & D)

63459-0303-XX HERZUMA 150MG Solution Reconstituted (Teva Pharmaceuticals USA)

63459-0305-XX HERZUMA 420MG Solution Reconstituted (Teva Pharmaceuticals USA)

63459-0307-XX HERZUMA 420MG Solution Reconstituted (Teva Pharmaceuticals USA)

67457-0845-XX OGIVRI 420MG Solution Reconstituted (MYLAN INSTITUTIONAL)

67457-0847-XX OGIVRI 420MG Solution Reconstituted (MYLAN INSTITUTIONAL)

67457-0991-XX OGIVRI 150MG Solution Reconstituted (MYLAN INSTITUTIONAL)

00069-0305-XX TRAZIMERA 420MG Solution Reconstituted (PFIZER U.S.)

00069-0306-XX TRAZIMERA 420MG Solution Reconstituted (PFIZER U.S.)

00069-0308-XX TRAZIMERA 150MG Solution Reconstituted (PFIZER U.S.)

55513-0132-XX KANJINTI 420MG Solution Reconstituted (AMGEN)

55513-0141-XX KANJINTI 150MG Solution Reconstituted (AMGEN)

DESCRIPTION

Trastuzumab is a recombinant DNA-derived IgG1 kappa monoclonal antibody that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2.  Trastuzumab has been shown to inhibit the proliferation of human tumor cells that overexpress HER2.  Trastuzumab is also a mediator of antibody-dependent cellular cytotoxicity (ADCC). Trastuzumab-mediated ADCC, a method of cancer cell destruction, is preferentially exerted on those cancer cells which overexpress HER2.

Biosimilar products are biological products that are highly similar to an existing FDA-approved innovator product and have no clinically meaningful differences from the innovator product.  The differences in the biosimilars must be proven to be in the clinically inactive components of the biosimilars, e.g., stabilizers or buffers.

At present, the FDA has approved five products biosimilar to trastuzumab: trastuzumab-anns (Kanjinti), trastuzumab-dkst (Ogivri), trastuzumab-dttb (Ontruzant®), trastuzumab-pkrb (Herzuma®) and Trastuzumab-qyyp (Trazimera).

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

NOTE: New to therapy or patients switching from Herceptin® require use of one of the preferred biosimilars before a non-preferred product except as outlined above.

Universal Criteria

Breast Cancer

Central Nervous System Cancer

Gastric, Esophageal, and Esophagogastric Junction Cancers

Uterine Cancer (Endometrial Carcinoma)

Colorectal Adenocarcinoma

Head and Neck Cancer

*HER2-positive overexpression criteria:

·         Immunohistochemistry (IHC) assay 3+

·         Dual-probe in situ hybridization (ISH) assay HER2/CEP17 ratio ≥ 2.0 AND average HER2 copy number ≥ 4.0 signals/cell

·         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+

  • HER2/CEP17 ratio < 2.0 AND average HER2 copy number ≥ 6.0 signals/cell AND concurrent IHC 2+ or 3+

  • HER2/CEP17 ratio < 2.0 AND average HER2 copy number ≥ 4.0 and < 6.0 signals/cell AND concurrent IHC 3+

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

RENEWAL CRITERIA

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Breast Cancer

Neo-adjuvant/Adjuvant Therapy

Combination Therapy

o    Administer an initial dose of 4 mg/kg intravenously followed by 2 mg/kg intravenously weekly during chemotherapy for up to 18 weeks.

o    One week following the last weekly dose of trastuzumab, administer 6 mg/kg intravenously every three weeks.

Single-Agent Therapy (following anthracycline therapy)

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

Note: Therapy should not exceed a total of 52 weeks of treatment.

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

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.

CNS Metastases from Breast Cancer

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.

Uterine Cancer

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.

Head and Neck Cancer

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.

LENGTH OF AUTHORIZATION

Coverage is provided for six months and may be renewed.

DOSING LIMITS

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

 

Indication

Loading Dose

(Billable Units)

Maintenance

(Billable Units)

Breast Cancer & Colorectal Cancer

o    7-day dosing schedule

o    21-day dosing schedule

 

45

90

 

30

75

Gastric/Esophageal/Gastro-Esophageal Junction Cancers

o    7-day dosing schedule

o    14-day dosing schedule

 

45

75

 

30

45

 

CNS Cancer (Leptomeningeal Metastases from Breast Cancer)

CNS Cancer (Limited/Extensive Brain Metastases), Uterine Cancer, and Head and Neck Cancer

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.     Herceptin [package insert]. South San Francisco, CA; Genentech, Inc; February 2021. Accessed February 2021.

2.     Ogivri [package insert]. Steinhausen, SZ; Mylan, Inc; December 2020. Accessed February 2021.

3.     Kanjinti [package insert]. Thousand Oaks, CA; Amgen, Inc; October 2019. Accessed February 2021.

4.     Trazimera [package insert]. Cork, Ireland; Pfizer Ireland, Inc; November 2020. Accessed February 2021.

5.     Herzuma [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Celltrion, Inc; May 2019. Accessed February 2021.

6.     Ontruzant [package insert]. Yeonsu-gu, Incheon, Republic of Korea; Samsung Bioepsis; March 2020. Accessed February 2021

7.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) trastuzumab. National Comprehensive Cancer Network, 2021. 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 February 2021.

8.     Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer 1.2021. National Comprehensive Cancer Network, 2021. 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 February 2021.

9.     Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer 2.2021. National Comprehensive Cancer Network, 2021. 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 February 2021.

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.

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, 2021. 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 February 2021.

31.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer 1.2021. National Comprehensive Cancer Network, 2021. 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 February 2021.

32.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer 4.2020. National Comprehensive Cancer Network, 2021. 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 February 2021.

33.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers 5.2020. National Comprehensive Cancer Network, 2021. 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 February 2021.

34.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms 1.2021. National Comprehensive Cancer Network, 2021. 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 February 2021.

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.

36.  Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273-1283.

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.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers 1.2021. National Comprehensive Cancer Network, 2021. 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 February 2021.

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

42.  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.

43.  Lexi-Comp Online. (2020). AHFS Dl. Trastuzumab. Retrieved December 2, 2020 from Lexi-Comp Online with AHFS.

44.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2020, October). Trastuzumab. Retrieved December 2, 2020 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  12/1/2016

MOST RECENT REVIEW DATE:    7/31/2021

ID_MRx

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