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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-J2000-52

Original Effective Date: 03/15/16

Reviewed: 02/08/17

Revised: 03/15/17

Next Review: 02/14/18

Subject: Irinotecan Liposome Injection (Onivyde™)

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   Previous Version
           

DESCRIPTION:

Irinotecan liposome injection (Onivyde) is a topoisomerase 1 inhibitor encapsulated in a lipid bilayer vesicle or liposome. Topoisomerase 1 promotes cytotoxicity by inducing single-strand breaks in DNA and preventing re-ligation. In mice, irinotecan liposome at lower doses has demonstrated similar intratumoral exposure as compared to irinotecan hydrochloride.

Irinotecan liposome injection (Onivyde) was approved by the U.S. Food and Drug Administration (FDA) in October 2015 in combination with 5-fluorouracil (5-FU) and leucovorin (LV), for the treatment of metastatic adenocarcinoma of the pancreas that has progressed after gemcitabine-based therapy.

The efficacy of irinotecan liposome injection was evaluated in a three-arm, randomized, open-label trial in patients with metastatic pancreatic adenocarcinoma with documented disease progression, after gemcitabine or gemcitabine-based therapy. Subjects were eligible for the trial if the Karnofsky Performance Status (KPS) was greater than or equal to 70, serum bilirubin was within normal limits, and albumin was greater than or equal to 3 g/dL. The subjects were randomized to receive irinotecan liposome injection monotherapy, irinotecan liposome injection with 5-FU/LV, or 5-FU/ LV alone. Treatment was continued until disease progression or unacceptable toxicity. The primary outcome of overall survival was improved with irinotecan liposome injection in combination with 5-FU/LV at 6.1 months as compared to 4.2 months with 5-FU/ LV alone (hazard ratio 0.68, 95%CI 0.50 – 0.93; p=0.014). There was no improvement in overall survival with irinotecan liposome injection when used as monotherapy as compared to 5-FU/ LV alone. Median progression-free survival was improved with irinotecan liposome injection in combination with 5-FU/LV at 3.1 months as compared to 1.5 months with 5-FU/ LV alone (hazard ratio 0.55, 95%CI 0.41 – 0.75). The objective response rate (confirmed complete/partial response) was also improved with irinotecan liposome injection in combination with 5-FU/LV at a rate of 7.7% as compared to 0.8% with 5-FU/ LV alone. The most frequent adverse reactions resulting in discontinuation of with irinotecan liposome injection in combination with 5-FU/LV were diarrhea, vomiting and sepsis. Dose reductions or delays in therapy most frequently occurred due to neutropenia, diarrhea, nausea, anemia, vomiting, fatigue, and thrombocytopenia.

POSITION STATEMENT:

Initiation of Irinotecan liposome injection (Onivyde) meets the definition of medical necessity when ALL of the following are met:

1. Diagnosis of metastatic adenocarcinoma of the pancreas

2. Disease has progressed following gemcitabine-based therapy

3. Irinotecan liposome injection (Onivyde) will be used in combination with both fluorouracil AND leucovorin

4. The dose does not exceed 70 mg/m2 every two weeks

Duration of approval: 6 months

Continuation of irinotecan liposome injection (Onivyde) meets the definition of medical necessity for the treatment of pancreatic cancer when ALL of the following criteria are met:

1. The member’s disease has not progressed while receiving treatment with irinotecan liposome injection (Onivyde)

2. 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

3. The dose does not exceed 70 mg/m2 every two weeks

Duration of approval: 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

For the treatment of metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy in combination with fluorouracil and leucovorin.

• Do not substitute irinotecan liposome injection for other drugs containing irinotecan HCl.

• The recommended dose is 70 mg/m2 intravenous infusion over 90 minutes every two weeks.

• Premedicate with a corticosteroid and an anti-emetic 30 minutes prior.

Dose Adjustments

• The recommended starting dose in patients homozygous for UGT1A1*28 is 50 mg/m2 every two weeks. Increase the dose to 70 mg/m2 as tolerated in subsequent cycles.

• There is no recommended dose for patients with serum bilirubin above the upper limit of normal.

• Dose reductions may be necessary. See prescribing information for details of adjustment in the setting of an adverse reaction by grade from the National Cancer Institute Common Terminology Criteria for Adverse Events.

Drug Availability

• Injection: 43 mg/10 mL single dose vial

PRECAUTIONS:

Boxed Warning

SEVERE NEUTROPENIA AND SEVERE DIARRHEA

• Fatal neutropenic sepsis occurred in 0.8% of patients receiving irinotecan liposome injection. Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving irinotecan liposome injection in combination with fluorouracil and leucovorin. Withhold irinotecan liposome injection for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment.

• Severe diarrhea occurred in 13% of patients receiving irinotecan liposome injection in combination with fluorouracil and leucovorin. Do not administer to patients with bowel obstruction. Withhold for diarrhea of Grade 2-4 severity. Administer loperamide for late diarrhea of any severity. Administer atropine, if not contraindicated, for early diarrhea of any severity.

Contraindications

• Severe hypersensitivity reaction to irinotecan liposome injection or irinotecan HCl.

Precautions/Warnings

• Interstitial lung disease (ILD): Fatal ILD has occurred in patients receiving irinotecan HCl. Discontinue irinotecan liposome injection if ILD is diagnosed.

• Severe hypersensitivity reaction: Permanently discontinue for severe hypersensitivity reactions.

• Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J9205

Injection, irinotecan liposome, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity

C25.0 – C25.9

Malignant neoplasm of pancreas

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) was found at the time of the guideline creation. The following Local Coverage Determination (LCD) was reviewed on the last guideline revised date: Irinotecan (L33727) located at fcso.com.

DEFINITIONS:

Table 1

Karnofsky Performance Status (KPS) (%)

Able to carry on normal activity and to work; no special care needed.

  100  

Normal no complaints; no evidence of disease.

90

Able to carry on normal activity; minor signs or symptoms of disease.

80

Normal activity with effort; some signs or symptoms of disease.

Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.

70

Cares for self; unable to carry on normal activity or to do active work.

60

Requires occasional assistance, but is able to care for most of his personal needs.

50

Requires considerable assistance and frequent medical care.

Unable to care for self; requires equivalent of institutional or hospital care; disease may be progressing rapidly.

40

Disabled; requires special care and assistance.

30

Severely disabled; hospital admission is indicated although death not imminent.

20

Very sick; hospital admission necessary; active supportive treatment necessary.

10

Moribund; fatal processes progressing rapidly.

0

Dead

RELATED GUIDELINES:

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

OTHER:

Table 2: Common Terminology Criteria for Adverse Events v4.0 (CTCAE)

Grade

Description

1

Mild; asymptomatic or mild symptoms; clinical diagnostic observations only; intervention not indicated

2

Moderate; minimal, local or noninvasive intervention indicated; limited age-appropriate instrumental activities of daily living

3

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living

4

Life-threatening consequences; urgent intervention indicated

5

Death related to adverse event

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.;2017 [cited 2017 Jan 18]. Available from: http://www.clinicalpharmacology.com/.
  2. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Jan 18]. Available from: http://www.thomsonhc.com/.
  3. National Cancer Institute. Common Terminology Criteria for Adverse Events. Available at: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed 1/15/16.
  4. National Comprehensive Cancer Network (NCCN). Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited2017 Jan 23] Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.
  5. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Version 2.2016. Pancreatic cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/pancreatic.pdf. Accessed 01/23/16.
  6. Onivyde [prescribing information]. Merrimack Pharmaceuticals, Inc. Cambridge, MS. February 2016.
  7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Jan 18]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 02/08/17.

GUIDELINE UPDATE INFORMATION:

03/15/16

New Medical Coverage Guideline.

04/01/16

Revision to guideline consisting of adding code C9474 and deleting code C9399.

01/01/17

Revision: added HCPCS code J9205.

03/15/17

Review and revision to guideline consisting of updating position statement, program exceptions, and references.

Date Printed: October 23, 2017: 02:16 AM