MEDICAL COVERAGE GUIDELINES SECTION: LABORATORY

ORIGINAL EFFECTIV E DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE:

11/26/13 06/21/16 02/02/15

GENETIC TESTING WITH CANCER SUSCEPTIBILITY PANELS USING NEXT GENERATION SEQUENCING

Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Medical Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Medical Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as “Description” defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as “Criteria” defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Medical Coverage Guidelines are subject to change as new information becomes available. For purposes of this Medical Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS®, BLUE SHIELD® and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ.

Description: Numerous genetic mutations are associated with certain types of hereditary cancer. Genetic cancer susceptibility panels using next generation sequencing (NGS) technology have been investigated for the analysis of multiple genes at one time as opposed to sequential, individual mutations. NGS uses massively parallel platforms to allow the sequencing of large stretches of DNA. Composition of the panels is variable, and different commercial products for the same condition may test a different set of genes. The make-up of the panels is determined by the specific lab that has developed the test. In addition, the composition of any individual panel is likely to change over time as new mutations are discovered and added to the existing panels. O863.5.docx

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MEDICAL COVERAGE GUIDELINES SECTION: LABORATORY

ORIGINAL EFFECTIV E DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE:

11/26/13 06/21/16 02/02/15

GENETIC TESTING WITH CANCER SUSCEPTIBILITY PANELS USING NEXT GENERATION SEQUENCING (cont.) Description: (cont.) Ambry Genetics Hereditary Cancer Panel Tests: Gene Tested APC ATM BARD1 BMPR1A BRCA1, BRCA2 BRIP1 CDH1 CDKN2A CDK4 CHEK2 EPCAM FH FLCN MET MITF MLH1 MRE11A MSH2 MSH6 MUTYH NBN NF1 PALB2 PMS2 PTEN RAD50 RAD51C RAD51D RET SDHA SDHAF2 SDHB SDHC SDHD SMAD4 STK11 TMEM127 TP53 TSC1, TSC2 VHL

BRCAplus

BreastNext

X X X

X

X

X X

X

X

X X X X X

X X X X

CancerNext

ColoNext

X X X X X

X

X X X X X X

X X X X X X X X X X X X X

GYNplus

Ov aNext

X X

PancNext

PGLNext

RenalNext

X X

X X

X

X

X X

X

X X X

X

X

X

X X X

X X

X X

X X

X X

X X X X X X X X X X X X X

X

X

X X X X X X

X X

X X

X X X

X X

X X X X X X X

X

X X

X X

X

X

X

X

X

X

X

X

X X X X

X

O863.5.docx

X

X X X

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X

MEDICAL COVERAGE GUIDELINES SECTION: LABORATORY

ORIGINAL EFFECTIV E DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE:

11/26/13 06/21/16 02/02/15

GENETIC TESTING WITH CANCER SUSCEPTIBILITY PANELS USING NEXT GENERATION SEQUENCING (cont.) Description: (cont.) GeneDx Hereditary Cancer Panel Tests: Gene Tested

APC ATM AXIN2 BARD1 BMPR1A BRCA1, BRCA2 BRIP1 CDH1 CDKN2A CDK4 CHEK2 EPCAM FANCC MLH1 MRE11A MSH2 MSH6 MUTYH NBN PALB2 PMS2 PTEN RAD50 RAD51C RAD51D SMAD4 STK11 TP53 VHL XRCC2

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Breast Cancer High Risk Panel

Breast / Ov arian Cancer Panel

X

Colorectal Cancer Panel

Comprehensive Cancer Panel

X X X

X X X

X

X

X X

X

X X

X X

X

X

X X X X X X X X

X X

X X X

X X

X X X X

X

X X X X

X X X X X

X X

X X X

X

X

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Endometrial Cancer Panel

Lynch / Colorectal Cancer High Risk Panel X

X

Pancreatic Cancer Panel X X

X

X X X X

X

X

X

X

X

X X X

X X X

X X X

X X

X X X

X X X

X

X X X X X X X

X

X X

X X X X

MEDICAL COVERAGE GUIDELINES SECTION: LABORATORY

ORIGINAL EFFECTIV E DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE:

11/26/13 06/21/16 02/02/15

GENETIC TESTING WITH CANCER SUSCEPTIBILITY PANELS USING NEXT GENERATION SEQUENCING (cont.) Description: (cont.) Other Labs: Gene Tested AKT1 APC ATM ATR AXIN2 BAP1 BARD1 BMPR1A BRCA1, BRCA2 BRIP1 CDH1 CDKN2A CDK4 CHEK1 CHEK2 CTNNA1 EPCAM FAM175A FAP GALNT12 GEN1 GREM1 HDGC HNPCC HOXB13 MAP MEN1 MLH1 MLH2 MLH3 MRE11A MSH2 MSH6 MUTYH NBN PALB2 PIK3CA PMS2 PPM1D PMS2 POLD1 POLE PRSS1

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Mayo Clinic

Myriad myRisk Hereditary Cancer Panel

X

X X

Univ ersity of Washington BROCA Breast Cancer Risk Panel X X X X

Univ ersity of Washington ColoSeq Gene Panel X X

X

X

X

X

X X X X X X X X

X

X X X X X X X X X X X X X X X X

X

X

X X X X X X

X X X

X

X X

X X

X X X X

X X X X X

X

X

X X X X X X X X X X X X

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X X X

X X

X X

MEDICAL COVERAGE GUIDELINES SECTION: LABORATORY

ORIGINAL EFFECTIV E DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE:

11/26/13 06/21/16 02/02/15

GENETIC TESTING WITH CANCER SUSCEPTIBILITY PANELS USING NEXT GENERATION SEQUENCING (cont.) Description: (cont.) Other Labs: (cont.) Gene Tested PTEN RAD50 RAD51 RAD51C RAD51D RET SDHB SDHC SDHD SMAD4 STK11 TP53 TP53BP1 VHL XRCC2

Mayo Clinic

Myriad myRisk Hereditary Cancer Panel

X

X

X X

X X X

X X X

Univ ersity of Washington BROCA Breast Cancer Risk Panel X X X X X X X X X X X X X X X

Univ ersity of Washington ColoSeq™ Gene Panel X

X X X

Definitions: Genetic Testing: Analysis of DNA, RNA, chromosomes, proteins and certain metabolites in order to detect alterations related to an inherited disorder. Gene: A hereditary unit consisting of segments of DNA that occupies a specific location on chromosomes. Genes undergo mutation when their DNA sequence changes. Genetic Counseling: Instruction that provides interpretation of genetic tests and information about courses of action that are available for the care of an individual with a genetic disorder or for future family planning. Affected Individual: An individual displaying signs or symptoms characteristic of a suspected or specific inherited disorder. Unaffected Individual: An individual who displays no signs or symptoms characteristic of a suspected or specific inherited disorder. Screening: Genetic screening is the testing of an individual with no symptoms for a specific inherited disorder to determine if the individual carries an abnormal gene. Screening can be used to predict risk or potential risk for the individual or their offspring. O863.5.docx Page 5 of 6

MEDICAL COVERAGE GUIDELINES SECTION: LABORATORY

ORIGINAL EFFECTIV E DATE: LAST REVIEW DATE: LAST CRITERIA REVISION DATE: ARCHIVE DATE:

11/26/13 06/21/16 02/02/15

GENETIC TESTING WITH CANCER SUSCEPTIBILITY PANELS USING NEXT GENERATION SEQUENCING (cont.) Criteria: Although genetic cancer susceptibility panels using next generation sequencing are considered investigational, there may be individual components of the panel that are medically necessary. Testing for individual components of a genetic panel may be medically necessary in some clinical situations. Other Medical Coverage Guidelines may apply to these individual components.  Genetic testing and/or counseling of an unaffected individual, regardless of risk factors is considered screening and not eligible for coverage.  Genetic testing and/or counseling of an affected individual to confirm a disease when confirmation of the diagnosis would not impact the care and/or management is considered not medically necessary and not eligible for coverage.  Genetic cancer susceptibility panels using next generation sequencing are considered experimental or investigational based upon: 1. Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and 2. Insufficient evidence to support improvement of the net health outcome, and 3. Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives.

Resources: Literature reviewed 05/12/15. We do not include marketing materials, poster boards and nonpublished literature in our review. The BCBS Association Medical Policy Reference Manual (MPRM) policy is included in our guideline review. References cited in the MPRM policy are not duplicated on this guideline. 1.

2.04.93 BCBS Association Medical Policy Reference Manual. Genetic Cancer Susc eptibility Panels Using Next Generation Sequencing. Re-issue date 05/19/2016, issue date 06/13/2013.

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