DECISIONDx BIOMARKER TESTS Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. 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. O607.12.docx Page 1 of 7
Description: DecisionDx tests (Castle Biosciences, Inc.) are proprietary biomarker based gene expression profile (GEP) tests that are being investigated to assist in prognosis and treatment of various cancers. DecisionDx tests include DecisionDx-EC for esophageal cancer, DecisionDx-GBM for glioblastoma multiforme, DecisionDx-Melanoma, DecisionDx-Mesothelioma, DecisionDx-Thymoma and DecisionDx- UM for uveal melanoma (also known as ocular or choroidal melanoma). Definitions: Gene Expression: The translation of the information encoded in a gene into messenger RNA (mrna) which may or may not then be translated into a protein. 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. O607.12.docx Page 2 of 7
Criteria: 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. Gene expression profiling for uveal melanoma with DecisionDx-UM is considered medically necessary for an individual with primary, localized uveal melanoma. Gene expression profiling DecisionDx biomarker tests for all other indications not previously listed or if above criteria not met 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, and 4. Insufficient evidence to support improvement outside the investigational setting. These biomarkers tests include, but are not limited to: DecisionDx-EC DecisionDx-GBM DecisionDx-Melanoma DecisionDx-Mesothelioma DecisionDx-Thymoma O607.12.docx Page 3 of 7
Resources: Literature reviewed 03/06/18. 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. 2.04.120 BCBS Association Medical Policy Reference Manual. Gene Expression Profiling for Uveal Melanoma. Re-issue date 02/08/18, issue date 05/22/2014. 2. 2.04.121 BCBS Association Medical Policy Reference Manual. Miscellaneous Genetic and Molecular Diagnostic Tests. Re-Issue date 07/13/17, Issue date 10/09/2014. 3. Allingham-Hawkins D, Lea A, Levine S. DecisionDx-GBM Gene Expression Assay for Prognostic Testing in Glioblastoma Multiform. PLoS Curr. 2010;2:RRN1186. 4. Berger AC, Davidson RS, Poitras JK, et al. Clinical impact of a 31-gene expression profile test for cutaneous melanoma in 156 prospectively and consecutively tested patients. Curr Med Res Opin. Jun 3 2016:1-6. 5. Castle Biosciences Incorporated. Development Efforts for DecisionDx-GBM, DecisionDx-UM, DecisionDx-LEA in USA. Accessed 08/06/2010. 6. Castle Biosciences Incorporated. About Castle Biosciences, Inc., In Development. Accessed 01/04/2012. 7. Colman H, Zhang L, Phillips HS, et al. Meta-analysis of gene expression profiling data from glioblastoma tumor samples identifies a robust multigene classifier predictive of survival. AACR Meeting Abstracts. 2006/4/1 (1):1337-c, 1338. 8. Colman H, Zhang L, Sulman EP, et al. A multigene predictor of outcome in glioblastoma. Neuro Oncol. 2010/1/1;12(1):49-57. 9. Cook RW, Middlebrook B, Wilkinson J, et al. Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients Assessing Genetic Expression Profiles in Melanoma Prognosis Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. Diagn Pathol. Feb 13 Feb 5 Oct Aug 29 2018;13(1):13. 10. Correa ZM, Augsburger JJ. Independent Prognostic Significance of Gene Expression Profile Class and Largest Basal Diameter of Posterior Uveal Melanomas. Am J Ophthalmol. Feb 2016;162:20-27 e21. O607.12.docx Page 4 of 7
Resources: (cont.) 11. Farberg AS, Glazer AM, Winkelmann RR, Rigel DS. Assessing Genetic Expression Profiles in Melanoma Prognosis. Dermatologic clinics. Oct 2017;35(4):545-550. 12. Gerami P, Cook RW, Russell MC, et al. Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy. J Am Acad Dermatol. May 2015;72(5):780-785 e783. 13. Gerami P, Cook RW, Wilkinson J, et al. Development of a prognostic genetic signature to predict the metastatic risk associated with cutaneous melanoma. Clin Cancer Res. Jan 1 2015;21(1):175-183. 14. Gokmen-Polar Y, Cook RW, Goswami CP, et al. A gene signature to determine metastatic behavior in thymomas. PLoS One. 2013;8(7):e66047. 15. Harbour JW. A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15- gene expression profile. Methods Mol Biol. 2014;1102:427-440. 16. Harbour JW, Chen R. The DecisionDx-UM Gene Expression Profile Test Provides Risk Stratification and Individualized Patient Care in Uveal Melanoma. PLoS Curr. 2013;5. 17. Hsueh EC, DeBloom JR, Lee J, et al. Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test. Journal of hematology & oncology. Aug 29 2017;10(1):152. 18. Nading MA, Balch CM, Sober AJ. Implications of the 2009 American Joint Committee on Cancer Melanoma Staging and Classification on dermatologists and their patients. Seminars in cutaneous medicine and surgery. Sep 2010;29(3):142-147. 19. Onken MD, Worley LA, Char DH, et al. Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma. Ophthalmology. Aug 2012;119(8):1596-1603. 20. Shan W, Davies R, Choudhary J, et al. Intended use for a neoadjuvant chemoradiation response prediction test for locally advanced esophageal adenocarcinoma: a survey analysis of thoracic surgeons in the US. Curr Med Res Opin. May 2015;31(5):1003-1007. 21. UpToDate.com. Tumor Node Metastasis (TNM) Staging and Other Prognostic Factors in Cutaneous Melanoma. 12/21/2016. 22. Zager JS, Gastman BR, Leachman S, et al. Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients. BMC cancer. Feb 5 2018;18(1):130. O607.12.docx Page 5 of 7
Non-Discrimination Statement: Blue Cross Blue Shield of Arizona (BCBSAZ) complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability or sex. BCBSAZ provides appropriate free aids and services, such as qualified interpreters and written information in other formats, to people with disabilities to communicate effectively with us. BCBSAZ also provides free language services to people whose primary language is not English, such as qualified interpreters and information written in other languages. If you need these services, call (602) 864-4884 for Spanish and (877) 475-4799 for all other languages and other aids and services. If you believe that BCBSAZ 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: BCBSAZ s Civil Rights Coordinator, Attn: Civil Rights Coordinator, Blue Cross Blue Shield of Arizona, P.O. Box 13466, Phoenix, AZ 85002-3466, (602) 864-2288, TTY/TDD (602) 864-4823, crc@azblue.com. You can file a grievance in person or by mail or email. If you need help filing a grievance BCBSAZ s 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, DC 20201, 1 800 368 1019, 800 537 7697 (TDD). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html Multi-Language Interpreter Services: O607.12.docx Page 6 of 7
Multi-Language Interpreter Services: (cont.) O607.12.docx Page 7 of 7