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Last Review Date: 03/05/2024

Date of Origin: 05/16/2013

Dates Reviewed: 07/2013, 11/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 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, 04/2019, 06/2019, 9/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020, 03/2021, 06/2021, 09/2021, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024

1. Length of Authorization ^1,7,15

Coverage will be provided for 6 months and may be renewed, unless otherwise specified.

• Adjuvant treatment in breast cancer is limited to 14 cycles (42 weeks total). (May be given for up to 17 cycles in patients who did not receive preoperative therapy).

2. Dosing Limits

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

• Kadcyla 100 mg single-dose vial: 1 vial every 21 days 
• Kadcyla 160 mg single-dose vial: 3 vials every 21 days

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

• 480 billable units every 21 days

3. 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], fam-trastuzumab deruxtecan-nxki, trastuzumab-hyaluronidase, pertuzumab/trastuzumab and hyaluronidase-zzxf, etc.); AND

Breast Cancer † ‡ ^1-4,7

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
  • Used as adjuvant therapy; AND
    • Patient has locally advanced or node positive disease ‡; AND
      • Used for residual disease following completion of planned chemotherapy and mastectomy or breast-conserving surgery (BCS); OR
      • Used in patients not considering pre-operative systemic therapy; OR
    • Patient has inflammatory breast cancer; AND

• Used in patients who had a response to preoperative systemic therapy, followed by surgery, and need to complete planned chemotherapy ‡; OR
• Patient has residual disease following preoperative therapy ‡; OR
• Patient has early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based therapy †; OR
• Patient has metastatic or recurrent unresectable disease OR inflammatory breast cancer with no response to preoperative systemic therapy; AND
  • Used as second-line therapy and beyond; OR
• Patient has metastatic disease that recurred during or within 6 months of completing adjuvant therapy †; AND

• • Patient previously received trastuzumab and a taxane, separately or in combination

Central Nervous System (CNS) Cancer ‡ ^2,13

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
• Used for the treatment of brain metastases in patients with breast cancer; AND
  • Used as initial treatment in patients with small asymptomatic brain metastases; OR
  • Used for relapsed limited brain metastases with either stable systemic disease or reasonable systemic treatment options; OR
  • Patient has recurrent limited brain metastases; OR
  • Used for recurrent extensive brain metastases with stable systemic disease or reasonable systemic treatment options

Non-Small Cell Lung Cancer (NSCLC) ‡ ^2,5,11

• Patient has ERBB2 (HER2) mutation positive disease as determined by an FDA-approved or CLIA-complaint testv; AND
• Used as subsequent therapy; AND
• Patient has recurrent, advanced, or metastatic disease (excluding locoregional recurrence or symptomatic local disease without evidence of disseminated disease) or mediastinal lymph node recurrence with prior radiation therapy

Head and Neck Cancer ‡ ^2,12,14

• Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant testv; AND
• Patient has salivary gland tumors; AND
• Used for one of the following:
  • • • Recurrent disease with distant metastases
      • Unresectable locoregional recurrence with prior radiation therapy (RT)
      • Unresectable second primary with prior RT

v If confirmed using an FDA-approved assay – http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1,5

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: left ventricular dysfunction, hepatotoxicity, pulmonary toxicity (i.e., interstitial lung disease, pneumonitis), thrombocytopenia, neurotoxicity, infusion-related and hypersensitivity reactions, hemorrhage, extravasation at infusion site, etc.; AND
• Left ventricular ejection fraction (LVEF) obtained within the previous 3 months as follows:
  • Metastatic or Recurrent Breast Cancer: LVEF is >45% OR LVEF is 40% to ≤45% and absolute decrease is <10% from baseline; OR
  • All other indications: LVEF is ≥50% OR LVEF is 45% to <50% and absolute decrease is <10% from baseline; AND

Breast Cancer (adjuvant treatment) ^1,7,15

• Patient has not exceeded a maximum of 14 cycles of therapy (42 weeks total). (May be given for up to 17 cycles in patients who did not receive preoperative therapy).

5. Dosage/Administration ^1,5,12,13,15

6. Billing Code/Availability Information

HCPCS Code:

• J9354 – Injection, ado-trastuzumab emtansine, 1 mg; 1 billable unit = 1 mg

NDC(s):

• Kadcyla 100 mg single-dose vial: 50242-0088-xx 
• Kadcyla 160 mg single-dose vial: 50242-0087-xx

7. References

1. Kadcyla [package insert]. South San Francisco, CA; Genentech, Inc.; February 2022. Accessed January 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) ado-trastuzumab emtansine. 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 January 2024.
3. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8; 367(19):1783-91.
4. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628.
5. Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with HER2 mutant lung cancers: Results from a phase II basket trial. J Clin Oncol. 2018 Aug 20;36(24):2532-2537. doi: 10.1200/JCO.2018.77.9777.
6. 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.

7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Breast Cancer, Version 1.2024. 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 January 2024.
8. 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.
9. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from https://www.hoparx.org/about-us/advocacy-awareness/issue-briefs/
10. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer, Version 1.2024. 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 January 2024.
12. Jhaveri KL, Wang XV, Luoh SW, et al. Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH trial (EAY131) subprotocol Q. Ann Oncol. 2019 Nov 1;30(11):1821-1830.
13. Montemurro F, Delaloge S, Barrios CH, et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial. Ann Oncol. 2020 Oct;31(10):1350-1358. doi: 10.1016/j.annonc.2020.06.020.
14. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Head and Neck Cancers, Version 1.2024. 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 October 2024.
15. Tolaney SM, Tayob N, Dang C, et al. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. J Clin Oncol. 2021 Jul 20;39(21):2375-2385. doi: 10.1200/JCO.20.03398. Epub 2021 Jun 2. PMID: 34077270.

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.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A

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