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Date Printed: August 23, 2017: 01:32 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-J1000-80

Original Effective Date: 12/15/12

Reviewed: 12/14/16

Revised: 01/15/17

Subject: Ziv-aflibercept (Zaltrap®) IV

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:

Colorectal cancer is the fourth most frequently diagnosed cancer and the second most frequent cause of cancer death in the United States. Current treatment of metastatic colorectal cancer involves various agents used either alone or in combination, including bevacizumab, capecitabine, irinotecan, oxaliplatin, panitumumab, regorafenib, ziv-aflibercept, or 5-fluorouracil/leucovorin.

Ziv-aflibercept (Zaltrap®) was approved by the U.S. Food and Drug Administration (FDA) on August 3, 2012 for use in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI) in metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen. Ziv-aflibercept inhibits angiogenesis by binding to vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factors 1 and 2.

Aflibercept (ziv-aflibercept in the United States) was assessed in combination with FOLFIRI in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. The combination significantly improved overall survival as compared to FOLFIRI alone (hazard ratio [HR], 0.817) with median survival times of 13.5 versus 12 months, respectively. Progression-free survival was also significantly improved (HR, 0.758) with median survival times of 6.9 versus 4.67 months, respectively.

POSITION STATEMENT:

I. Initiation of ziv-aflibercept (Zaltrap®) meets the definition of medical necessity when ALL of the following criteria are met:

A. Member is diagnosed with colon or rectal cancer

B. Member has metastatic or unresectable advanced disease

C. Member has previously received therapy containing ONE of the following:

1. Oxaliplatin (e.g. FOLFOX, CapeOX)

2. 5-fluorouracil/leucovorin

3. Capecitabine

D. Member has not previously received therapy with irinotecan

E. Use will be in combination with ONE of the following:

1. FOLFIRI (5-fluorouracil, leucovorin, irinotecan)

2. irinotecan

F. 7. The dose does not exceed 4 mg/kg every 2 weeks

Duration of approval: 6 months

II.Continuation of ziv-aflibercept (Zaltrap®) meets the definition of medical necessity for colon or rectal cancer when the following criteria are met:

A. The member’s disease has not progressed while receiving treatment with ziv-aflibercept

B. The member has been previously approved by Florida Blue or another health plan in the past 2 years, OR the member has previously met all indication-specific criteria for coverage

C. The dose does not exceed 4 mg/kg every 2 weeks

Approval duration: 1 year

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

4 mg/kg as an intravenous infusion over 1 hour every 2 weeks

Drug Availability

100 mg/4 mL (25 mg/mL), 200 mg/8 mL (25 mg/mL) single-use vials

PRECAUTIONS:

Boxed Warning

• Hemorrhage: Severe and sometimes fatal hemorrhage, including gastrointestinal (GI) hemorrhage, has been reported. Do not administer in patients with severe hemorrhage.

• Gastrointestinal Perforation: Discontinue if patient experiences perforation.

• Compromised Wound Healing: Suspend for at least 4 weeks prior to elective surgery, and do not resume for at least 4 weeks following major surgery and until the surgical wound is fully healed.

Contraindications

None

Precautions/Warnings

• Fistula Formation: Discontinue if fistula occurs.

• Hypertension: Monitor blood pressure and treat hypertension. Suspend temporarily if hypertension is not controlled. Discontinue if hypertensive crisis develops.

• Arterial Thromboembolic Events (e.g. transient ischemic attacks, cerebrovascular accident, angina pectoris). Discontinue if arterial thromboembolic events occur.

• Proteinuria: Monitor urine protein. Suspend use when proteinuria is greater than or equal to 2 grams in 24 hours. Discontinue if nephrotic syndrome or thrombotic microangiopathy develops.

• Neutropenia and Neutropenic Complications: Delay administration until neutrophil count is greater than or equal to 1.5 x 109/L.

• Diarrhea and Dehydration: Incidence of severe diarrhea and dehydration is increased and elderly patients should be monitored closely.

• Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue use if RPLS occurs.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J9400

Injection, ziv-aflibercept, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity (Effective 10/01/15):

C17.0 – C17.2

Malignant neoplasm of small intestine including duodenum, jejunum and ileum

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0 – C18.9

Malignant neoplasm of colon

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.8

Malignant neoplasm of overlapping sites of rectum, anus and anal canal

C78.00C78.02

Secondary malignant neoplasm of unspecified lung

C78.6

Secondary malignant neoplasm of retroperitoneum and peritoneum

C78.7

Secondary malignant neoplasm of liver and intrahepatic bile duct

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

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

DEFINITIONS:

None

RELATED GUIDELINES:

Bevacizumab (Avastin®) Injection, 09-J000-66
Capecitabine (Xeloda®) Tablets, 09-J1000-42

Human EGFR Inhibitors (cetuximab; panitumumab) IV, 09-J0000-94

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

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

Ramucirumab (Cyramza™) Injection, 09-J2000-14

Regorafenib (Stivarga®) IV, 09-J1000-83

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2016 [cited 2016 Nov 21]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2016 Nov 21]. Available from: http://www.clinicalpharmacology.com/.
  3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2014 Nov 15]. Available from: http://clinicaltrials.gov/.
  4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Nov 21]. Available from: http://www.thomsonhc.com/.
  5. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Colon Cancer, v.1.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Rectal Cancer, v.1.2017 [cited 2016 Nov 28]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  7. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [2016 Nov 28]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  8. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 Nov 21]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  9. Sanofi-Aventis U.S. LLC. Zaltrap (ziv-aflibercept) solution, concentrate. June 2016 [cited 2016 Nov 21]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f6725df6-50ee-4b0a-b900-d02ba634395d/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 12/14/16.

GUIDELINE UPDATE INFORMATION:

12/15/12

New Medical Coverage Guideline.

01/01/14

Revision to guideline; consisting of code update.

01/15/14

Review and revision to guideline; consisting of revising and reformatting description, position statement, dosage/administration, precautions/warning, exceptions and references.

01/15/15

Review and revision to guideline; consisting of updating references.

11/01/15

Revision: ICD-9 Codes deleted.

01/15/16

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

01/15/17

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

Date Printed: August 23, 2017: 01:32 PM