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Date Printed: October 20, 2017: 02:07 PM

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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-J1000-75

Original Effective Date: 09/15/12

Reviewed: 03/08/17

Revised: 04/15/17

Subject: Pertuzumab (Perjeta™) Injection

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.

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

DESCRIPTION:

Pertuzumab is a monoclonal antibody that antagonizes human epidermal growth factor receptor 2 protein (HER2). As a result, pertuzumab inhibits intracellular signaling through two major signal pathways. Inhibition of these signaling pathways can result in cell growth arrest and apoptosis. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity (ADCC). While pertuzumab alone inhibits the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab (Herceptin®) significantly increases anti-tumor activity in HER2-overexpressing tumors. Pertuzumab and trastuzumab bind to different epitopes of HER2 receptor and have complementary mechanisms of action.

Pertuzumab was initially granted approval for the treatment of HER-2 positive metastatic breast cancer in combination with trastuzumab (Herceptin®) and docetaxel (Taxol®). In September 2013, the approval was expanded to include treatment in the neoadjuvant setting. Similar to use in the metastatic setting, pertuzumab should be used in combination with trastuzumab and docetaxel.

National Comprehensive Cancer Network guidelines for Breast Cancer (version 2.2016) recommend use of pertuzumab in the neoadjevent, adjuvant, and metastatic setting. The role of pertuzumab in more than one line of therapy for the same individual (e.g., used in the neoadjuvant setting and in metastatic setting in a person who relapses) has not been clearly defined.

POSITION STATEMENT:

Initiation of pertuzumab (Perjeta™) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has been diagnosed with ONE of the following:

a. Locally advanced, inflammatory, or early stage breast cancer

b. Metastatic breast cancer

c. Recurrent 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. Pertuzumab will be used in combination ANY of the following:

a. Trastuzumab (Herceptin) with or without cytotoxic therapy (eg, vinorelbine or taxane) for one line of therapy beyond first-line therapy in patients previously treated with chemotherapy and trastuzumab in the absence of pertuzumab

b. Trastuzumab (Herceptin) and paclitaxel

c. Trastuzumab (Herceptin) and docetaxel

d. Trastuzumab (Herceptin) and docetaxel and carboplatin

4. Member has not received prior treatment with pertuzumab in any setting (e.g., neoadjuvant, primary) for any stage of disease (e.g., early, metastatic, recurrent)

5. Dose does not exceed EITHER of the following:

a. Initial: 840 mg x 1 dose

b. Maintenance: 420 mg every 21 days

Approval duration: 6 months

Continuation of pertuzumab (Perjeta™) meets the definition of medical necessity for 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. If indication for use is neoadjuvant treatment of early stage breast cancer, member has received fewer than 6 cycles of pertuzumab

3. Dose does not exceed 420 mg 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 indications

Pertuzumab is FDA-approved for the following indications:

  1. Treatment of HER2-positive metastatic breast cancer (MBC) in persons who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease when used in combination with trastuzumab and docetaxel
  2. Neoadjuvant treatment ofHER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer when used in combination with trastuzumab and docetaxel

Pertuzumab should be administered as an intravenous (IV) infusion. The initial dose is 840 mg IV over 60 minutes, followed by 420 mg IV every three weeks over 30-60 minutes.

Dose Modification

Withhold pertuzumab (and trastuzumab) dose for 3 weeks or more for either of the following

  1. A drop in left-ventricular ejection fraction (LVEF) to less than 45%
  2. LVEF of 45%-49% with a 10% or greater absolute decrease below pretreatment values

Pertuzumab may be resumed if the LVEF has recovered to greater than 49% or to 45% to 49% associated with less than a 10% absolute decrease below pretreatment values. If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, or has declined further, pertuzumab and trastuzumab should be discontinued, unless the benefits for the individual patient are deemed to outweigh the risks

Drug availability: pertuzumab is supplied as a 420 mg/14 mL single-use vial

PRECAUTIONS:

BOXED WARNING

  1. Cardiomyopathy: pertuzumab can result in subclinical and clinical cardiac failure manifesting as CHF and decreased LVEF. Evaluate cardiac function prior to and during therapy. Please refer to dosage/administration section for dose modifications for confirmed decreases in LVEF.
  2. Embryo-fetal toxicity: exposure to pertuzumab can result in embryo-fetal death and birth defects.

WARNINGS/PRECAUTIONS

  1. Infusion-Related Reactions: Monitor for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies.
  2. Hypersensitivity Reactions/Anaphylaxis: Monitor for signs and symptoms. If a severe hypersensitivity reaction/anaphylaxis occurs, discontinue the infusion immediately and administer appropriate medical therapies.

BILLING/CODING INFORMATION:

HCPCS Coding

J9306

Injection, pertuzumab, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity

C16.0 – C16.9

Malignant neoplasm of stomach

C50.011

Malignant neoplasm of nipple and areola, right female breast

C50.012

Malignant neoplasm of nipple and areola, left female breast

C50.019

Malignant neoplasm of nipple and areola, unspecified female breast

C50.021

Malignant neoplasm of nipple and areola, right male breast

C50.022

Malignant neoplasm of nipple and areola, left male breast

C50.029

Malignant neoplasm of nipple and areola, unspecified male breast

C50.111

Malignant neoplasm of central portion of right female breast

C50.112

Malignant neoplasm of central portion of left female breast

C50.119

Malignant neoplasm of central portion of unspecified female breast

C50.121

Malignant neoplasm of central portion of right male breast

C50.122

Malignant neoplasm of central portion of left male breast

C50.129

Malignant neoplasm of central portion of unspecified male breast

C50.211

Malignant neoplasm of upper-inner quadrant of right female breast

C50.212

Malignant neoplasm of upper-inner quadrant of left female breast

C50.219

Malignant neoplasm of upper-inner quadrant of unspecified female breast

C50.221

Malignant neoplasm of upper-inner quadrant of right male breast

C50.222

Malignant neoplasm of upper-inner quadrant of left male breast

C50.229

Malignant neoplasm of upper-inner quadrant of unspecified male breast

C50.311

Malignant neoplasm of lower-inner quadrant of right female breast

C50.312

Malignant neoplasm of lower-inner quadrant of left female breast

C50.319

Malignant neoplasm of lower-inner quadrant of unspecified female breast

C50.321

Malignant neoplasm of lower-inner quadrant of right male breast

C50.322

Malignant neoplasm of lower-inner quadrant of left male breast

C50.329

Malignant neoplasm of lower-inner quadrant of unspecified male breast

C50.411

Malignant neoplasm of upper-outer quadrant of right female breast

C50.412

Malignant neoplasm of upper-outer quadrant of left female breast

C50.419

Malignant neoplasm of upper-outer quadrant of unspecified female breast

C50.421

Malignant neoplasm of upper-outer quadrant of right male breast

C50.422

Malignant neoplasm of upper-outer quadrant of left male breast

C50.429

Malignant neoplasm of upper-outer quadrant of unspecified male breast

C50.511

Malignant neoplasm of lower-outer quadrant of right female breast

C50.512

Malignant neoplasm of lower-outer quadrant of left female breast

C50.519

Malignant neoplasm of lower-outer quadrant of unspecified female breast

C50.521

Malignant neoplasm of lower-outer quadrant of right male breast

C50.522

Malignant neoplasm of lower-outer quadrant of left male breast

C50.529

Malignant neoplasm of lower-outer quadrant of unspecified male breast

C50.611

Malignant neoplasm of axillary tail of right female breast

C50.612

Malignant neoplasm of axillary tail of left female breast

C50.619

Malignant neoplasm of axillary tail of unspecified female breast

C50.621

Malignant neoplasm of axillary tail of right male breast

C50.622

Malignant neoplasm of axillary tail of left male breast

C50.629

Malignant neoplasm of axillary tail of unspecified male breast

C50.811

Malignant neoplasm of overlapping sites of right female breast

C50.812

Malignant neoplasm of overlapping sites of left female breast

C50.819

Malignant neoplasm of overlapping sites of unspecified female breast

C50.821

Malignant neoplasm of overlapping sites of right male breast

C50.822

Malignant neoplasm of overlapping sites of left male breast

C50.829

Malignant neoplasm of overlapping sites of unspecified male breast

C50.911

Malignant neoplasm of unspecified site of right female breast

C50.912

Malignant neoplasm of unspecified site of left female breast

C50.919

Malignant neoplasm of unspecified site of unspecified female breast

C50.921

Malignant neoplasm of unspecified site of right male breast

C50.922

Malignant neoplasm of unspecified site of left male breast

C50.929

Malignant neoplasm of unspecified site of unspecified male breast

C56.1

Malignant neoplasm of right ovary

C56.2

Malignant neoplasm of left ovary

C56.9

Malignant neoplasm of unspecified ovary

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 Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

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.

DPD: deoxypyridinoline, also called D-Pyrilinks or Pyrilinks-D, is a crosslink of type I collagen present in bone which is excreted unmetabolized in urine and is a specific marker of bone resorption. It is measured in a urine tests in members when osteoporosis is suspected.

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

Neoadjuvant treatment: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy

RELATED GUIDELINES:

Ado-trastuzumab emtansine (Kadcyla) Injection, 09-J1000-90
Docetaxel (Taxotere®) IV, 09-J0000-95

Trastuzumab (Herceptin®) Injection, 09-J0000-86

OTHER:

None.

REFERENCES:

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2017. URL www.clinicalpharmacilogy-ip.com Accessed 1/28/17.
  2. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 1/28/2017.
  3. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 1/28/2017.
  4. National Comprehensive Cancer Network. Clinical Practice Guidelines Breast Cancer. Version 2.2016. Accessed 1/28/2017.
  5. Perjeta (pertuzumab) [package insert]. Genentech, Inc. South San Francisco (CA): September 2013.
  6. Pertuzumab. In McEvoy GK, editor. AHFS drug information 2015 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2015 [cited Jan 28 2015].

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 3/8/17.

GUIDELINE UPDATE INFORMATION:

09/15/12

New Medical Coverage Guideline.

12/15/12

Revision to guideline; consisting of adding criteria to define HER2 positive.

04/15/13

Review and revision to guideline; consisting of updating position statement to allow treatment beyond first-line, update precautions and references.

12/15/13

Revision to guideline; consisting of updating position statement.

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, dosage/administration, and precautions section; updating references and related guidelines.

04/15/15

Review and revision to guideline; consisting of revising position statement, references, definitions, program exceptions

08/15/15

Revision to guideline; consisting of revision position statement, coding

09/15/15

Revision to guideline; consisting of updating coding

11/01/15

Revision: ICD-9 Codes deleted.

04/15/16

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

07/15/16

Revision to guideline; consisting of updating position statement.

4/15/17

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

Date Printed: October 20, 2017: 02:07 PM