Humana Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors - Medicare Advantage Form

Please refer to CMS website for the most current applicable CMS Online Manual System (IOMs)/National Coverage Determination (NCD)/ Local Coverage Determination (LCD)/Local Coverage Article (LCA)/ Transmittals. Type NCD LCD LCA LCD LCA Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 2 of 20 Title ID Number Jurisdiction Medicare Administrative Contractors (MACs) Applicable States/Territories Next Generation Sequencing (NGS) Lab: Special Histochemical Stains and Immunohistochemical Stains 90.2 L36805 MolDX: MGMT Promoter Methylation Analysis MolDX: Molecular Diagnostic Tests (MDT) MolDX: Next-Generation Sequencing for Solid Tumors MolDX: NRAS Genetic Testing Billing and Coding: MolDX: know error® Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms Molecular Pathology Procedures L37001 L36807 L38158 L36797 A55172 L37810 L35000 Billing and Coding: Molecular Pathology Procedures A56199 Response to Comments: Molecular Pathology Procedures MolDX: MGMT Promoter Methylation Analysis A59383 L36113 J5, J8 - Wisconsin Physicians Service Insurance Corporation IA, IN, KS, MI, MO, NE J6, JK - National Government Services, Inc. CT, IL, ME, MA, MN, NH, NY, RI, VT, WI LCD LCA MolDX: Molecular Diagnostic Tests (MDT) MolDx: Next-Generation Sequencing for Solid Tumors MolDX: NRAS Genetic Testing L36021 L38067 L35442 J15 - CGS Administrators, LLC KY, OH Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 3 of 20 Billing and Coding: MolDX: know error® Lab: Special Histochemical Stains and Immunohistochemical Stains A54273 L36351 MolDX: MGMT Promoter Methylation Analysis MolDX: Molecular Diagnostic Tests (MDT) MolDX: Next-Generation Sequencing for Solid Tumors MolDX: NRAS Genetic Testing Billing and Coding: MolDX: know error® Lab: Special Histochemical Stains and Immunohistochemical Stains MolDX: MGMT Promoter Methylation Analysis MolDX: Molecular Diagnostic Tests (MDT) MolDX: Next-Generation Sequencing for Solid Tumors MolDX: NRAS Genetic Testing L36188 L35160 L38119 L36335 A55274 L36353 L36192 L36256 L38121 L36339 Billing and Coding: MolDX: Know error® Biomarkers for Oncology A55275 L35396 Biomarkers Overview Billing and Coding: Molecular Pathology and Genetic Testing Lab: Special Histochemical Stains and Immunohistochemical Stains L35062 A58917 L35922 LCD LCA LCD LCA LCD LCA JE - Noridian Healthcare Solutions, LLC CA, HI, NV, American Samoa, Guam, Northern Mariana Islands JF - Noridian Healthcare Solutions, LLC AK, AZ, ID, MT, ND, OR, SD, UT, WA, WY JH, JL - Novitas Solutions, Inc. AR, CO, DE, LA, MD, MS, NJ, NM, OK, PA, TX, D.C. Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 4 of 20 LCD LCA MolDX: MGMT Promoter Methylation Analysis MolDX: Molecular Diagnostic Tests (MDT) MolDX: Next-Generation Sequencing for Solid Tumors MolDX: NRAS Genetic Testing Billing and Coding: MolDX: know error® L35974 L35025 L38045 L35073 A53554 LCD Molecular Pathology Procedures L34519 JJ, JM - Palmetto GBA AL, GA, NC, SC, TN, VA, WV JN - First Coast Service Options, Inc. (Part A/B MAC) FL, PR, U.S. VI Description Comprehensive genomic profiling (CGP) (also referred to as comprehensive molecular profiling) is a type of somatic (tumor) test that involves a combination of laboratory methodologies to detect genetic alterations and the simultaneous evaluation of large numbers (hundreds to thousands) of biomarkers in tumor tissue to aid in the management of advanced solid tumors, including guiding treatment decisions as well as determination of clinical trial eligibility. Techniques can vary from test to test and may include next- generation sequencing (NGS), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) and often provides information on tumor mutational burden (TMB), microsatellite instability (MSI) and homologous recombination deficiency (HRD). Examples include Altera Tumor Genomic Profiling, Guardant360, NeoGenomics Solid Tumor NGS Fusion Panel and TissueNext. Some CGP tests analyze both deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). NeoTYPE DNA & RNA – Lung is an NGS profiling test that detects single nucleotide variants, insertions/deletions, copy number variants, and/or RNA fusions in a total of 50 genes (44 genes analyzed by DNA and 19 by RNA), plus MSI and TMB. Tempus xT is another example of a CGP somatic test performed for the management of advanced cancer. Previously Tempus xT conducted sequencing for both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) within a single panel. However, a new test, Tempus xR, is now available as an independent assay dedicated solely to RNA sequencing. This means that Tempus xT focuses on DNA analysis while Tempus xR specializes in RNA analysis, and they are no longer combined into one test. Single gene testing can be utilized to diagnose and monitor cancer including, but may not be limited to, cholangiocarcinoma, gallbladder cancer, gastrointestinal stromal tumor, glioblastoma, melanoma and thyroid cancer. This type of testing is indicated for an individual who exhibits disease symptoms and may be necessary to diagnose or rule out suspected cancer. Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 5 of 20 DNA Specimen Provenance Assignment (DSPA) Testing (eg, know error System) is a molecular diagnostic test intended for the protection and control of tissue samples to purportedly decrease the incidence of diagnostic mistakes due to the misidentification, specimen transposition or cell contamination of samples, also known as specimen provenance complications (SPCs). Breast and prostate tissues are most often tested but other tissue types, such as bone marrow, may also be examined. Coverage Determination Humana follows the CMS requirements that only allows coverage and payment for services that are reasonable and necessary for the diagnosis and treatment of illness or injury or to improve the functioning of a malformed body member except as specifically allowed by Medicare. Genetic tests must demonstrate clinical utility, analytical and clinical validity and fulfill the CMS “reasonable and necessary” criteria. Analytic validity (test accurately identifies the gene variant), clinical validity (test identifies or predicts the clinically defined disorder) and clinical utility (test measurably improves clinical outcomes) of the genetic test is supported by generally accepted standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, specialty society recommendations, and views of physicians practicing in relevant clinical areas. The test must be ordered by a physician who is treating the beneficiary and the results will be used in the management of a beneficiary’s specific medical problem. For jurisdictions with no Medicare guidance for a particular test, Humana will utilize the MolDX program and Technical Assessments for molecular assays as the standard to evaluate clinical utility, analytical and clinical validity in conjunction with adhering to Medicare’s reasonable and necessary requirement. In interpreting or supplementing the criteria above and in order to determine medical necessity consistently, Humana may consider the following criteria: Comprehensive Genomic Profiling for Solid Tumors Comprehensive genomic profiling (CGP) for solid tumors will be considered medically reasonable and necessary when the following requirements are met:44 • Analytic validity, clinical validity and clinical utility of the genetic test is supported by the MolDX program; AND • The test is ordered by a treating physician; AND • ALL of the following: o Cancer that has returned (recurrent or relapsed), cancer that does not respond to treatment (refractory), cancer that has spread from original site to another part of the body (metastatic) or advanced stages III or IV cancer; AND Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 6 of 20 o Individual has not been previously tested using the same comprehensive genomic profiling test for the same primary diagnosis; AND o Decision to seek further cancer treatment (eg, therapeutic chemotherapy) Criteria for Single Gene Testing IDH1 (81120) and/or IDH2 (81121) gene analysis will be considered medically reasonable and necessary for the following indications: • Cholangiocarcinoma that is locally advanced, metastatic or unresectable disease (IDH1 only);71 OR • Gallbladder cancer that is metastatic or unresectable disease (IDH1 only);71 OR • Glioblastoma15 KIT (c-KIT) gene analysis will be considered medically reasonable and necessary to guide therapeutic decision making43 when for the following indications: • Gastrointestinal stromal tumor (GIST) (81272);15 OR • Melanoma, metastatic or unresectable (81272)15 MGMT promoter methylation testing (81287) will be considered medically reasonable and necessary to guide therapeutic decision making43 for the following indications: • Glioblastoma;15 OR • Neuroendocrine tumors15 NRAS gene analysis (81311) will be considered medically reasonable and necessary for the following indications: • Metastatic colorectal cancer when needed to determine if a Medicare covered therapy is a reasonable option given the individual’s specific clinical presentation;15,37,38,39,40,41 OR • Metastatic melanoma;15 OR • Thyroid carcinoma15 PDGFRA gene analysis (81314) will be considered medically reasonable and necessary to guide therapeutic decision making43 when an individual presents with a mass known or clinically suspected to be GIST.13 TERT gene analysis (81345) will be considered medically reasonable and necessary for glioblastoma.13,15 Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 7 of 20 The use of the criteria in this Medicare Advantage Medical Coverage Policy provides clinical benefits highly likely to outweigh any clinical harms. Services that do not meet the criteria above are not medically necessary and thus do not provide a clinical benefit. Medically unnecessary services carry risks of adverse outcomes and may interfere with the pursuit of other treatments which have demonstrated efficacy. Coverage Limitations US Government Publishing Office. Electronic code of federal regulations: part 411 – 42 CFR § 411.15 - Particular services excluded from coverage The following tests may not be considered a benefit (statutory exclusion): • Tests performed to measure the quality of a process, including DNA Specimen Provenance Assignment (DSPA) testing to decrease specimen provenance complications (SPC) (eg, know error System) (81265)7,8,9,10,11,12 • Tests considered screening in the absence of clinical signs and symptoms of disease that are not specifically identified by the law;88 OR • Tests that confirm a diagnosis or known information;88 OR • Tests to determine risk for developing a disease or condition;88 OR • Tests performed to measure the quality of a process;88 OR • Tests without diagnosis specific indications;88 OR • Tests identified as investigational by available literature and/or the literature supplied by the developer and are not a part of a clinical trial88 These treatments and services fall within the Medicare program’s statutory exclusion that prohibits payment for items and services that have not been demonstrated to be reasonable and necessary for the diagnosis and treatment of illness or injury (§1862(a)(1) of the Act). Other services/items fall within the Medicare program’s statutory exclusion at 1862(a)(12), which prohibits payment. The following items will not be considered medically reasonable and necessary: • Genetic tests that have not demonstrated clinical utility, analytical and clinical validity via the MolDX Program • TERT mutation testing for melanoma Comprehensive Genomic Profiling and Genetic Testing for Solid Tumors Page: 8 of 20 A review of the current medical literature shows that the evidence is insufficient to determine that these services are standard medical treatments. There remains an absence of randomized, blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of these services in clinical management. The following items will not be considered medically reasonable and necessary: • CGP RNA sequencing as a stand-alone test without MolDX approval (eg, Tempus xR) A review of the current medical literature shows that there is no evidence to determine that this service is standard medical treatment. There is an absence of randomized, blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of this service in clinical management. Summary of Evidence Tempus xR Tempus xR is now offered as a stand-alone test, separate from Tempus xT. In the past, Tempus xT sequenced both RNA and DNA in a single panel but now Tempus xR focuses solely on RNA and Tempus xT is dedicated to DNA analysis. Most CGP tests typically analyze both DNA and RNA in a single panel and there is insufficient evidence for RNA-only CGP. The validity of analysis, its clinical relevance and utility are yet to be established in published, peer-reviewed medical literature. TERT Mutation Testing for Melanoma A systematic review and meta-analysis investigation the connection between somatic mutations in the TERT gene promoter and melanoma survival revealed limited yet suggestive evidence of an adverse impact of TERT mutations on the survival of an individual diagnosed with melanoma. The authors gathered data from 19 independent studies and found that individuals with TERT-mutated melanoma had a significantly worse overall survival compared to wild-type mutations.58