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Date Printed: August 23, 2017: 05:58 AM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J1000-90

Original Effective Date: 05/15/13

Reviewed: 03/08/17

Revised: 04/15/17

Subject: Ado-trastuzumab emtansine (Kadcyla™)

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Ado-trastuzumab emtansine (Kadcyla™) is an anti-body-drug conjugate comprising trastuzumab and emtansine. In February 2013, ado-trastuzumab emtansine was approved by the US Food and Drug Administration (FDA) for the treatment of persons with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Emtansine is a sulfur-containing derivative of the potent microtubule inhibitor, maytansine. Emtansine is conjugated to trastuzumab by lysine side chains, forming a stable thioether linker. Ado-trastuzumab emtansine binds HER2 with an affinity comparable to that of trastuzumab (Herceptin) and is the fourth anti-HER2 therapy currently approved by the FDA for the treatment of HER2-positive breast cancer.

The HER tyrosine kinase receptor family includes four transmembrane receptors (HER1/epidermal growth factor receptor [EGFR], HER2, HER3, and HER4) that mediate cell growth, survival, and differentiation. HER receptors activate intracellular signaling pathways. In 20% to 30% of breast tumors, the HER2 gene is amplified and overexpressed, leading to altered regulation of tumor cell growth, proliferation, and survival. The approval of ado-trastuzumab emtansine was based primarily on the results of a phase III, randomized, multicenter, active-controlled study, EMILIA. The study included 991 subjects with unresectable locally advanced or metastatic HER2-positive breast cancer previously treated with trastuzumab and a taxane.

Subjects were randomized to one of two groups:

• Ado-trastuzumab emtansine 3.6 mg/kg every 21 days

• Oral lapatinib 1250 mg daily + capecitabine 1000 mg/m2 every 12 hours for the first 14 days of each 21 day treatment cycle

The primary efficacy endpoints were progression-free survival (PFS) and overall survival (OS). The PFS in the ado-trastuzumab emtansine-treated group was extended by 3.2 months when compared to that of the comparator arm (9.6 months vs. 6.4 months, respectively; HR=0.65, 95% CI 0.55-0.77, p<0.001). The median OS was also significantly greater in subjects randomized to the ado-trastuzumab group compared to that of the comparator arm (30.9 months vs. 25.1 months, respectively; HR=0.68, 95% CI 0.55-0.85, p<0.001).

Ado-trastuzumab is included in the National Comprehensive Cancer Network (NCCN) Breast Cancer Guidelines (Version 2.2016).

POSITION STATEMENT:

Initiation of ado-trastuzumab emtansine (Kadcyla™) meets the definition of medical necessity when ALL of the following criteria are met:

1. Indication for use is treatment of recurrent or metastatic breast cancer

2. Member has HER2-positive disease documented by ONE of the following – laboratory documentation must be provided:

a. Immunohistochemistry (IHC) is 3+

b. Fluorescent in situ hybridization (FISH) HER2 gene copy is greater than 6

c. FISH ratio of HER2 gene/chromosome 17 ratio is greater than or equal to 2.0

3. Member has received prior therapy with a trastuzumab (Herceptin) –based regimen

4. Ado-trastuzumab emtansine is used as monotherapy

5. Member has not received ado-trastuzumab emtansine as part of another line of therapy (i.e., previously exposed to ado-trastuzumab emtansine, disease progressed, and drug was discontinued)

6. Dose does not exceed 3.6 mg/kg every 21 days

7. Member is 18 years if age or older

Approval duration: 6 months

Continuation of ado-trastuzumab emtansine (Kadcyla™) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue or another health plan in the past two years for treatment of breast cancer, OR the member has previously met all indication-specific initiation criteria

2. Member’s disease has not progressed during treatment with ado-trastuzumab emtansine

3. Dose does not exceed 3.6 mg/kg every 21 days

Approval duration: 6 months

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: ado-trastuzumab emtansine is indicated as monotherapy for the treatment of persons with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Individuals should have either 1) received prior therapy for metastatic disease 2) developed disease recurrence during or within six months of completing adjuvant therapy. The recommended dose is 3.6 mg/kg given as in intravenous (IV) infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity occurs.

• 1st infusion: Administer over 90 minutes. Observe for signs and symptoms of infusion-related reactions during and for at least 90 minutes following infusion.

• Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated. Observe for signs and symptoms of infusion-related reactions during and for at least 30 minutes following infusion.

Dose Adjustments

Management of increased serum transaminases, hyperbilirubinemia, left ventricular dysfunction, thrombocytopenia, pulmonary toxicity or peripheral neuropathy may require temporary interruption, dose reduction or treatment discontinuation. Refer to prescribing information for detailed dose adjustments.

Drug Availability: ado-trastuzumab emtansine is supplied as a single-use vial containing 100- or 160 mg per vial.

PRECAUTIONS:

Boxed Warning

• Ado-trastuzumab emtansine should not be substituted for or with trastuzumab

• Hepatotoxicity, liver failure, and death have occurred in ado-trastuzumab emtansine-treated subjects; hepatic function should be monitored prior to therapy initiation and prior to each subsequent doses. Dose adjustment or permanent discontinuation of therapy may be required.

• Therapy may lead to reductions in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation. Monitor and withhold dosing or discontinue as appropriate.

• Pregnancy Category D: can cause fetal harm. Females should be advised of potential risk to the fetus.

Warnings/Precautions

• Pulmonary toxicity: permanently discontinue ado-trastuzumab emtansine in persons diagnosed with interstitial lung disease or pneumonitis.

• Infusion related reactions: monitor for signs and symptoms during and after infusion. If significant infusion-related reactions or hypersensitivity reactions occur, slow or interrupt the infusion and administer appropriate medical therapies. Permanently discontinue therapy if a life-threatening infusion-related reaction occurs.

• Thrombocytopenia: monitor platelet counts prior to each dose. Institute dose modifications as appropriate.

• Neurotoxicity: monitor for signs and symptoms. Withhold dosing temporarily for persons experiencing Grade 3 or 4 peripheral neuropathy

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J9354

Injection, ado-trastuzumab emtansine, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity

C50.011 – C50.929

Malignant neoplasm of female and male breast

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time this guideline was drafted.

DEFINITIONS:

Adjuvant Treatment: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will return. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biologic therapy. Adjuvant therapy can be used after or in combination with another form of cancer therapy and is commonly used following removal of a cancerous tumor to further help in treatment.

Metastatic cancer: when cancer spreads from the primary site (place where it started) to other places in the body.

RELATED GUIDELINES:

Capecitabine (Xeloda®) Tablets, 09-J1000-42
Carboplatin (Paraplatin®) IV, 09-J0000-93

Docetaxel (Taxotere®) IV, 09-J0000-95

Doxorubicin HCl Liposome (Doxil®) IV, 09-J0000-91

Gemcitabine (Gemzar®), 09-J0000-96

Irinotecan HCl Camptosar®) IV, 09-J0000-99

Lapatinib (Tykerb®) Tablets, 09-J-1000-47

Oxaliplatin (Eloxatin®) IV, 09-J1000-00

Paclitaxel and Nab-Paclitaxel IV, 09-J1000-05

Pertuzumab (Perjeta™) IV, 09-J1000-75

Vinorelbine (Navelbine®) IV, 09-J1000-03

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015 Jan 28]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017 Jan 28]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2017 Jan 28]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Jan 28]. Available from: http://www.thomsonhc.com/.
  5. Genetech, Inc Kadcyla (ado-trastuzumab emtansine ) [package insert]
  6. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 2017 Jan 28]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Jan 28]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  8. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. NEJM 2012;367(19): 1783-91.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 03/08/17.

GUIDELINE UPDATE INFORMATION:

05/15/13

New Medical Coverage Guideline.

10/15/13

Revision to guideline; consisting of administrative action to update coding

01/01/14

Revision to guideline; consisting of code update.

04/15/14

Review and revision to guideline; consisting of revising and reformatting position statement and updating references.

12/15/14

Revision to guideline; consisting of updating position statement.

04/15/15

Review and revision to guideline; consisting of description, position statement, program exceptions, dosage/administration, references.

04/15/16

Review and revision to guideline; description, position statement, coding, references.

04/15/17

Review and revision to guideline; description, position statement, references.

Date Printed: August 23, 2017: 05:58 AM