BlueCross BlueShield of Tennessee Medical Policy Manual

Ado-Trastuzumab Emtansine

NDC CODE(S)

50242-0088-xx Kadcyla 100 MG SOLR (GENENTECH)

 

50242-0087-xx Kadcyla 160 MG SOLR (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.

REFER TO DECISION SUPPORT TREE

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

*HER2 positive overexpression criteria
  • Immunohistochemistry (IHC) assay 3+

  • Fluorescence in situ hybridization (FISH) assay ≥2.0 (HER2/CEP17 ratio

  • Average HER2 copy number ≥ 6 signals/cell

RENEWAL CRITERIA

INDICATION(S) DOSAGE & ADMINISTRATION
Metastatic breast cancer 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle)

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).

No controlled studies were found in the published literature that validate the use of ado-trastuzumab emtansine for the treatment of other diseases or conditions.

SOURCES

BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2015). Ado-trastuzumab emtansine (trastuzumab-DM1) for treatment of HER2-positive malignancies (5.01.22). Retrieved September 14, 2016 from BlueWeb.

Lexi-Comp Online. (2017, March). AHFS DI. Ado-trastuzumab emtansine. Retrieved March 15, 2017 from Lexi-Comp Online with AHFS.

MICROMEDEX Healthcare Series. Drugdex Evaluations. (2017, February). Ado-trastuzumab emtansine. Retrieved March 15, 2017 from MICROMEDEX Healthcare Series.  

National Comprehensive Cancer Network. (2017). NCCN Drugs & Biologics Compendium™. Ado-trastuzumab emtansine. Retrieved March 15, 2017 from the National Comprehensive Cancer Network.

U. S. Food and Drug Administration. (2016, July). Center for Drug Evaluation and Research. Kadcyla® (ado-trastuzumab emtansine) for injection, for intravenous use. Retrieved March 15, 2017 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125427s096lbl.pdf.

ORIGINAL EFFECTIVE DATE:  3/8/2013

MOST RECENT REVIEW DATE:  6/6/2017

ID_MRx

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.

Pharmaceutical Decision Support Tree

Ado-Trastuzumab Emtansine (Kadcyla  ®

  1. Is this the initial request for this agent?

If yes, go to question #2

If no, go to question #7

  1. Does the individual have a diagnosis of metastatic or recurrent breast cancer that is HER-2 positive (i.e., tumors overexpress the human epidermal growth-factor receptor-2 protein)?

If yes, go to question #3

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the disease ANY ONE of the following?

If yes, go to question #4

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is there documentation of a baseline left ventricular ejection fraction (LVEF) that is >45%?

If yes, go to question #5

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for treatment as single agent?

If yes, go to question #6

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the request for 460 billable units or less every 21 days for dosage of 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) over 6 months?

If yes, this meets medical necessity and/or medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Does the individual continue to meet the initial approval criteria in questions 2 through 6?

If yes, go to question #8

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is tumor response indicated with stabilization of disease or decrease in size of tumor?

If yes, go to question #9

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Was there absence of unacceptable toxicity from the agent, e.g., hepatotoxicity; left ventricular dysfunction; pulmonary toxicity (i.e. pneumonitis); thrombocytopenia; neurotoxicity; infusion-related and hypersensitivity reactions?

If yes, go to question #10

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is the left ventricular ejection fraction (LVEF) >45% OR is LVEF ≥40% and decrease is <10% from baseline (results must be less than 3 months old)?

If yes, this meets medical necessity and/or medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.