Ado-Trastuzumab Emtansine (Kadcyla®)
50242-0088-XX KADCYLA 100MG Solution Reconstituted (GENENTECH)
50242-0087-XX KADCYLA 160MG Solution Reconstituted (GENENTECH)
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
Ado-trastuzumab emtansine for the treatment of the following is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Non-Small Cell Lung Cancer
Head and Neck Cancer
Salivary Gland Tumors
Ado-trastuzumab emtansine for the treatment of other conditions/diseases is considered investigational.
Patient at least 18 years of age; AND
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
Patient has human epidermal growth factor receptor 2 (HER2)-positive* disease as determined by an FDA-approved or CLIA-compliant test ❖; AND
Used as single agent therapy; 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
Used as adjuvant therapy in patients with:
Locally advanced residual or node positive
disease following completion of planned chemotherapy and mastectomy
or lumpectomy; OR
Early breast cancer with residual invasive disease after neoadjuvant taxane and trastuzumab-based therapy; OR
Patient has metastatic or recurrent disease
Non-Small Cell Lung Cancer
Salivary Gland Tumors
Patient has recurrent disease that is unresectable, with distant metastasis, or second primary
❖ 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:
Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in initial approval criteria; 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 the following: 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) within the previous 3 months as follows:
Metastatic or Recurrent Breast Cancer: >45% OR LVEF is ≥40% and absolute decrease is <10% from baseline; OR
All other indications: Left ventricular ejection fraction (LVEF) is ≥ 50% OR LVEF is ≥45% and absolute decrease is <10% from baseline; AND
Adjuvant treatment of breast cancer is limited to 14 cycles (42 weeks total)
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.
Use as adjuvant treatment of HER2-positive disease in individuals with locally advanced or early breast cancer with residual disease is limited up to 14 cycles (42 week’s total).
Max Units (per dose and over time) [HCPCS Unit]:
480 billable units every 21 days
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.
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.
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).
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
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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