Last Review Date: 06/06/2022

Date of Origin: 02/04/2020

Dates Reviewed: 02/2020, 06/2020, 09/2020, 02/2021, 03/2022, 06/2022

I. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

II. Dosing Limits

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

• Enhertu 100 mg vial: 7 vials every 21 days 

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

• Breast Cancer: 600 billable units every 21 days
• All other indications: 700 billable units every 21 days

III. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• 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
• Used as a single agent; AND
• Therapy will not be substituted with or for any trastuzumab-based formulation (i.e., trastuzumab [or trastuzumab biosimilar product], ado-trastuzumab emtansine, trastuzumab-hyaluronidase, pertuzumab/trastuzumab and hyaluronidase-zzxf, etc.); AND

Breast Cancer † ‡ ^{1,2,4,8,15,16}

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
• Patient has recurrent unresectable (local or regional) or metastatic disease OR inflammatory breast cancer with no response to preoperative systemic therapy; AND
  • • Used as subsequent therapy; OR
    • Used as first-line therapy in patients with who experience disease progression during or within 6 months of neoadjuvant or adjuvant therapy (12 months for pertuzumab-containing regimens)

Gastric, Esophageal, and Esophagogastric Junction Cancers † ‡ Ф ^1,2,9,17,18

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
• Patient has adenocarcinoma histology; AND
• Patient is not a surgical candidate OR has unresectable locally advanced, recurrent, or metastatic disease; AND
• Used as subsequent therapy

Colorectal Cancer (CRC) ‡ ^2,10-12

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; 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

Appendiceal Adenocarcinoma – Colon Cancer ‡ ^2,11

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; 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

Non-Small Cell Lung Cancer (NSCLC) ‡ ^2,13,14

• Patient has ERBB2 (HER2) mutation positive disease as determined by an FDA-approved or CLIA-complaint testv; AND
• Patient has metastatic disease

     vIf confirmed using an FDA approved assay - http://www.fda.gov/companiondiagnostics

† FDA approved indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug (only applies to Gastric and Esophagogastric Junction Cancers)

IV. Renewal Criteria ^1,10,13

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: pulmonary toxicity (e.g., interstitial lung disease, pneumonitis), neutropenia/febrile neutropenia, left ventricular dysfunction/symptomatic congestive heart failure, etc.; AND
• Left ventricular ejection fraction (LVEF) within the previous 3 months as follows:
  • LVEF is > 45% and absolute decrease is ≤ 20% from baseline; OR
  • LVEF is 40% to 45% and absolute decrease is < 10% from baseline

V. Dosage/Administration ^1,11-13

VI. Billing Code/Availability Information

HCPCS Code:

• J9358 – Injection, fam-trastuzumab deruxtecan-nxki, 1 mg: 1 billable unit = 1 mg

NDC:

• Enhertu 100 mg single-dose vial: 65597-0406-xx 

VII. References

1. Enhertu [package insert]. Basking Ridge, NJ; Daiichi Sankyo, Inc; May 2022. Accessed May 2022.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) fam-trastuzumab deruxtecan-nxki. 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 May 2022.
3. 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.

4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer, Version 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.
5. 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.
6. 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
7. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
8. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2019 Dec 11. Doi: 10.1056/NEJMoa1914510.
9. Shitara K, Bang YJ, Iwasa S, et al; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430.
10. Siena S, Di Bartolomeo M, Raghav KPS, et al. A phase II, multicenter, open-label study of trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01. J Clin Oncol 2020;38(suppl; abstr 4000).
11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Colon Cancer, 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 May 2022.
12. 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 May 2022.
13. Smit EF, Nakagawa K, Nagasaka M, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): interim results of DESTINY-Lung01[abstract]. J Clin Oncol 2020;38:Abstract 9504.
14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer, Version 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.
15. 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.
16. Cortés J, Kim SB, Chung WP, et al; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.
17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Esophageal and Esophagogastric Junction Cancers, Version 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.
18. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Gastric Cancer, Version 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.
19. 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.
20. 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 May 2022.

Appendix 1 – Covered Diagnosis Codes

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

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) 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/LCD/LCA):