BlueCross BlueShield of Tennessee Medical Policy Manual

Ado-Trastuzumab Emtansine (Kadcyla®)

NDC CODE(S)

50242-0088-XX KADCYLA 100MG Solution Reconstituted (GENENTECH)

50242-0087-XX KADCYLA 160MG Solution Reconstituted (GENENTECH)

DESCRIPTION

Ado-trastuzumab emtansine is an antibody-drug conjugate. It consists of the anti-HER2 IgG1 antibody trastuzumab covalently linked to the drug DM1 via the stable thioether linker MCC.  DM1 is a maytansine derivative.  

Maytansine, an ansamycin antibiotic, is a potent microtubule inhibitor which has not been found to have a clinical use due to severe side effects and lack of tumor specificity. The term emtansine references both the source drug and the covalent linker of the small molecule complex MCC-DM1.

In the body, ado-trastuzumab emtansine binds to the HER2 receptor on cancer cells.  It is then internalized into the cell where it causes lysosomal degradation resulting in the intracellular release of DM1-containing cytotoxic catabolites.  These bind to tubulin causing disruption of the cellular microtubule network resulting in cell cycle arrest and apoptotic cell death.  Ado-trastuzumab emtansine additionally appears to inhibit HER2 receptor signaling, mediate antibody-dependent cell-mediated cytotoxicity and inhibit shedding of the HER2 extracellular domain in human breast cancer cells that overexpress HER2, as is found with trastuzumab

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

Universal Criteria:

Breast Cancer

Non-Small Cell Lung Cancer

 

Salivary Gland Tumors

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

 

*HER2 positive overexpression criteria:  

·         Immunohistochemistry (IHC) assay 3+; OR

·         Dual-probe in situ hybridization (ISH) assay HER2/CEP17 ratio ≥ 2.0 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+

RENEWAL CRITERIA

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Adjuvant therapy of locally advanced or early stage breast cancer

3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) for up to 14 cycles unless there is disease recurrence or unmanageable toxicity.  

Metastatic or recurrent breast cancer, NSCLC, Salivary Gland Tumors

3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity

LENGTH OF AUTHORIZATION

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

DOSAGE LIMITS

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

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 e National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

1.    1.     Kadcyla [package insert]. South San Francisco, CA; Genentech, Inc; September 2020. Accessed January 2021.

2.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) ado-trastuzumab emtansine. 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 January 2021.

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 in patients with HER2 mutant lung cancers: Results from a phase II basket trial. J Clin Oncolo 2017, 35: Abstract 8510.

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 56.2020. National Comprehensive Cancer Network,2020. 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 2020.

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 http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf

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 v2.2021. 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 January 2021.

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.  Lexi-Comp Online. (2021, February). AHFS DI. Ado-trastuzumab emtansine. Retrieved March 16, 2021 from Lexi-Comp Online with AHFS.

14.  MICROMEDEX Healthcare Series. Drugdex Evaluations. (2021, January). Ado-trastuzumab emtansine. Retrieved March 16, 2021 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  3/8/2013

MOST RECENT REVIEW DATE:    7/31/2021

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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