Highmark Commercial Medical Policy - Pennsylvania

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Medical Policy: L-167-004
Topic: UGT1A1 Targeted Mutation Analysis for Irinotecan Response
Section: Laboratory
Effective Date: November 13, 2017
Issue Date: November 13, 2017
Last Reviewed: June 2017

Targeted mutation analysis of the UGT1A1 gene sequence by polymerase chain reaction (PCR) identifies any mutation in the region. The results are reported as negative, heterozygous or homozygous.

  • Negative = UGT1A1 6/6 (*1/*1) genotype; Wild-type genotype; No UGT1A1*28 mutation is identified. Low risk of severe toxicity from standard initial dosages of irinotecan.
  • Heterozygous = UGT1A1 6/7 (*1/*28) genotype; One wild-type allele and one UGT1A1*28 mutation allele identified. Increased risk for irinotecan toxicity, but initial standard doses may be still be tolerated.
  • Homozygous = UGT1A1 7/7 (*28/*28) genotype. Increased risk for severe toxicity from standard initial doses of irinotecan, thus irinotecan product labeling recommends considering a reduced initial dose.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

UGT1A1 testing may be considered medically necessary in individuals with metastatic and/or recurrent colorectal cancer prior to the initiation of irinotecan therapy.

Procedure Codes

Professional Statements and Societal Positions

In May 2010, the FDA announced a safety change to the prescribing information for Camptosar® (irinotecan) Injection:

  • When administered in combination with other agents, or as a single agent, a reduction in the starting dose by at least one level of Camptosar® should be considered for patients known to be homozygous for the UGT1A1*28 allele. However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment."

A laboratory test is available to determine the UGT1A1 status of patients. Testing can detect UGT1A1 6/6, 6/7, 7/7 genotypes."

UGT1A1 *28 testing for irinotecan is recognized by the FDA as a valid genomic biomarker.

Guidelines for genetic testing have not been established by organizations such as the National Comprehensive Cancer Network (NCCN) and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. However, both organizations recognize the availability and utility of testing UGT1A1 *28 prior to treatment with irinotecan

The NCCN states the following:

  • Also, a warning was added to the label for irinotecan indicating that a reduced starting dose of the drug should be used in patients known to be homozygous for UGT1A1*28.”
  • “A practical approach to the use of UGT1A1*28 allele testing with respect to patients receiving irinotecan has been presented, although guidelines for the use of this test in clinical practice have not been established.”
  • "UGT1A1 testing on a patient who has experienced irinotecan toxicity is not recommended since that patient will require a dose reduction regardless of the GT1A1 test result."

Place of Service: Outpatient

UGT1A1 targeted mutation analysis is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
    • Qualified sign language interpreters
    • Written information in other formats (large print, audio, accessible electronic formats, other formats)
  • Provides free language services to people whose primary language is not English, such as:
    • Qualified interpreters
    • Information written in other languages
If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

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Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

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