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Date Printed: June 23, 2017: 11:42 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-J2000-46

Original Effective Date: 1/15/16

Reviewed: 12/13/16

Revised: 01/15/17

Next Review: 12/13/17

Subject: Trifluridine-Tipiracil (Lonsurf®) Capsule

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:

Trifluridine is a thymidine-based nucleoside analog that inhibits cell proliferation of cancer cells by interference with DNA synthesis. Tipiracil prevents degradation of trifluridine through inhibition of its metabolism by thymidine phosphorylase and increases trifluridine exposure. Trifluridine and tipiracil demonstrated activity in fluorouracil resistant tumors and both KRAS wild-type and mutant human colorectal cancer xenografts in mice.

Trifluridine and tipiracil (Lonsurf®) was FDA approved in September 2015 for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Trifluridine and tipiracil was evaluated in a phase III, double blind study of 800 patients with adenocarcinoma of the colon or rectum. Patients were eligible for the study if they had received at least two prior regimens of chemotherapy which included a fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab and if KRAS wild-type tumors, cetuximab or panitumumab. The median overall survival with trifluridine and tipiracil was 7.1 months as compared to 5.3 months with placebo and the hazard ratio for death was 0.68 (p<0.001). The median progression-free survival was 2 months with trifluridine and tipiracil as compared to 1.7 months. The hazard ratio for progression was 0.48 (p<0.001).

The National Comprehensive Cancer Network (NCCN) guidelines for colon and rectal cancer support the use of trifluridine and tipiracil for unresectable advanced or metastatic disease not previously treated with the agent. NCCN recommends use after first disease progression following FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) with or without bevacizumab in patients with disease positive for the KRAS/NRAS mutation. NCCN also supports the use of trifluridine and tipiracil for second disease progression following treatment with irinotecan- and oxaliplatin-based regimens as well as FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) with or without bevacizumab (in patients with mutant or wild type tumors). The NCCN guidelines also support use in patients whose disease has progressed through all available regimens.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

I. Initiation of trifluridine and tipiracil (Lonsurf®) meets the definition for medical necessity for the following indications when the dosage does not exceed 35 mg/m2/dose twice daily based on trifluridine component (maximum of 80 mg of trifluridine component per dose) on days 1 through 5 and days 8 through 12 of a 28 day cycle:

A. Colon or Rectal Cancer and ALL of the following are met:

1. Trifluridine and tipiracil (Lonsurf®) will be used as a single agent

2. Member has metastatic or unresectable advanced disease

3. Member has not previously received trifluridine and tipiracil (Lonsurf®)

4. Member meets ONE of the following:

a. Trifluridine and tipiracil (Lonsurf®) is used following disease progression with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, irinotecan) +/- bevacizumab AND the member’s disease is positive for the KRAS/NRAS mutation

b. Trifluridine and tipiracil (Lonsurf®) is used as third-line or subsequent (i.e., fourth line or greater) therapy for disease progression after previous treatment with THREE or more of the following agents (combination use or in separate regimens):

i. Anti-EGFR therapy* (e.g., panitumumab or cetuximab) if KRAS/NRAS gene is normal (i.e., without mutation, also known as wild type).

ii. Anti-VEGF therapy* (e.g., bevacizumab, ziv-aflibercept or ramucirumab).

iii. Fluoropyrimidine-containing chemotherapy (e.g., fluorouracil or capecitabine).

iv. Irinotecan-containing chemotherapy

v. Oxaliplatin-containing chemotherapy

vi. Regorafenib (Stivarga®)

Duration of approval: 180 days

II. Continuation of trifluridine and tipiracil (Lonsurf®) 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 trifluridine and tipiracil (Lonsurf®)

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 35 mg/m2/dose twice daily based on trifluridine component (maximum of 80 mg of trifluridine component per dose) and is prescribed on days 1 through 5 and days 8 through 12 of a 28 day cycle

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

Trifluridine and tipiracil is indicated for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

The recommended starting dose is 35 mg/m2 up to a maximum of 80 mg (trifluridine component) orally twice daily. The dose should be taken within 1 hour after completion of morning and evening meals on days 1-5 and days 8-12 of each 28 day cycle until disease progression or unacceptable toxicity. The dose should be rounded to the nearest 5 mg increment.

Special handling and disposal procedures are recommended due to cytotoxicity.

Dose Adjustments

Do not initiate therapy until:

Withhold therapy within a treatment cycle for any of the following:

After recovery, resume therapy after reducing the dose by 5 mg/m2/dose from the previous dose level if the following occur:

A maximum of 3 dose reductions are permitted to a minimum dose of 20 mg/m2 twice daily. Do not escalate the dose after it has been reduced.

Drug Availability

PRECAUTIONS:

Contraindications

Precautions/Warnings

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals

J8999

Prescription drug, oral, chemotherapeutic, NOS

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

C17.0

Malignant neoplasm of duodenum

C17.1

Malignant neoplasm of jejunum

C17.2

Malignant neoplasm of ileum

C17.8

Malignant neoplasm of overlapping sites of small intestine

C17.9

Malignant neoplasm of small intestine, unspecified

C18.0

Malignant neoplasm of cecum

C18.1

Malignant neoplasm of appendix

C18.2

Malignant neoplasm of ascending colon

C18.3

Malignant neoplasm of hepatic flexure

C18.4

Malignant neoplasm of transverse colon

C18.5

Malignant neoplasm of splenic flexure

C18.6

Malignant neoplasm of descending colon

C18.7

Malignant neoplasm of sigmoid colon

C18.8

Malignant neoplasm of overlapping sites of colon

C18.9

Malignant neoplasm of colon, unspecified

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.8

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

C78.00 – 78.02

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 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 of the guideline creation.

DEFINITIONS:

VEGF - Vascular endothelial growth factor.

EGFR - Epidermal growth factor receptor.

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

KRAS Mutation Analysis, 05-86000-28

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

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

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

Ziv-aflibercept (Zaltrap®) IV, 09-J1000-80

OTHER:

Table 1: 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 [database online]. Tampa, FL: Gold Standard, Inc; 2016. URL www.clinicalpharmacilogy-ip.com Accessed 11/21/16.
  2. Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015; 372: 1909-1919.
  3. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 11/21/16.
  4. 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 11/18/15.
  5. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 11/28/16.
  6. 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.
  7. 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.
  8. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016[cited 2016 Nov 28]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  9. Lonsurf® (trifluridine and tipiracil) [package insert]. Taiho Oncology, Inc. Princeton (NJ): September 2015.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

01/15/16

New Medical Coverage Guideline.

05/15/16

Updated position statement with self-administration statement.

01/15/17

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

Date Printed: June 23, 2017: 11:42 AM