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Pharmacogenetic testing for the BRAF (V600E) mutation in tumor tissue for select individuals for treatment with vemurafenib (Zelboraf®)
Pharmacogenetic Testing to Determine Drug Sensitivity
The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.
Title: Pharmacogenetic Testing for the BRAF (V600E) Mutation in Tumor Tissue for Select Individuals for Treatment with Vemurafenib (Zelboraf
Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.
Pharmacogenetic testing for the BRAF (V600E) mutation in tumor tissue for select individuals for treatment with vemurafenib (Zelboraf
) is medically necessary and, therefore, covered for individuals with stage IIIC or IV melanoma for treatment with vemurafenib (Zelboraf®).
Testing for the BRAF(V600E) mutation for all other indications, including but not limited to, use in individuals with lesser-stage melanoma (ie, <stage IIIC or IV), or with non-melanoma tumors, is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.
The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.
The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
There is no Medicare coverage determination addressing this service; therefore, the Company policy is applicable.
Subject to the terms and conditions of the applicable Evidence of Coverage, pharmacogenetic testing for the BRAF (V600E) mutation in tumor tissue for select individuals for treatment with vemurafenib (Zelboraf
) is covered under the medical benefits of the Company's Medicare Advantage products when the medical necessity criteria listed in the medical policy are met.
Subject to the terms and conditions of the applicable Evidence of Coverage, BRAF (V600E) mutation tissue for all other indications, including but not limited to, use in individuals with melanoma < IIIC, or with non-melanoma tumors, is not eligible for payment under the medical benefits of the Company's Medicare Advantage products because the service is considered experimental/investigational.
Services that are experimental/investigational are excluded from the Company's Medicare Advantage products. Therefore, they are not eligible for reimbursement consideration.
US FOOD AND DRUG ADMINISTRATION STATUS
Genetic testing is a laboratory procedure and is historically not regulated by the US Food and Drug Administration (FDA). Clinical Laboratory Improvement Amendments (CLIA) establishes quality standards for all laboratory testing. However, recently, the FDA is reported to be involved in the evaluation of the service of genetic testing.
Mutations in the BRAF gene can be either inherited or acquired. Some inherited BRAF mutations will cause birth defects. Acquired mutations (oncogenes) are found in many cancers, including colorectal, malignant melanoma, Non-Hodgkin's lymphoma, non-small-cell lung carcinoma, and others. More than 30 different BRAF mutations associated with various cancers have been identified.
Many individuals with advanced melanoma have a mutation in the BRAF gene. A phase III clinical trial of the drug vemurafenib given to individuals with advanced melanoma who had the BRAF V600E mutation reported benefit in overall survival and progression-free survival for those in the vemurafenib (Zelboraf®) treatment group. These results, which were also corroborated with earlier clinical trials, support both the clinical validity and the clinical utility of the cobas 4800 BRAF V600 Mutation Test, a companion test for vemurafenib (Zelboraf®). The use of this test to select appropriate individuals for treatment with vemurafenib (Zelboraf®) results in improved outcomes when compared to the usual standard of care, dacarbazine (DTIC, DIC, Imidazole Carboxamide, DTIC-Dome®).
Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). BRAF gene mutation testing to select melanoma patients for BRAF inhibitor therapy. TEC Assessments 2011; Volume 26,
Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma.
Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib (Zelboraf®) in melanoma with BRAF V600E mutation.
N Engl J Med.
Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change?
King AJ, Patrick DR, Batorsky RS, et al. Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885.
Joseph EW, Pratilas CA, Poulikakos PI, et al. The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner.
Proc Natl Acad Sci U S A.
Ribas A, Kim KB, Schuchter LM, et al. BRIM-2: An open-label, multicenter phase II study of vemurafenib (Zelboraf®) in previously treated patients with BRAF V600E mutation-positive metastatic melanoma.
J Clin Oncol.
2011;29 (Suppl):Abstract 8509.
Sondergaard JN, Nazarian R, Wang Q, et al. Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032.
J Transl Med.
Takle AK, Brown MJ, Davies S, et al. The identification of potent and selective imidazole-based inhibitors of B-Raf kinase.
Bioorg Med Chem Lett.
Teutsch SM, Bradley LA, Palomaki GE, et al. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group.
Vultur A, Villanueva J, Herlyn M. Targeting BRAF in advanced melanoma: a first step toward manageable disease.
Clin Cancer Res.
Yang H, Higgins B, Kolinsky K, et al. RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models.
Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.
The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.
In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.
Code Number and Code Narrative
G0452 Molecular pathology procedure; physician interpretation and report
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