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BRAF Testing for Colorectal Cancer Lab Management Guidelines v2.0.2019 BRAF Testing for Colorectal Cancer MOL.TS.133.A v2.0.2019 Introduction BRAF testing for colorectal cancer is addressed by this guideline. Procedures addressed The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements. Procedures addressed by this Procedure codes guideline BRAF V600 targeted mutation analysis 81210 BRAF sequencing 81406 What is BRAF Definition BRAF is a gene that forms a part of a cell-signaling pathway to help control cell growth. Changes or mutations in the BRAF gene can cause out of control cell growth, which may lead to cancer.1 The most common BRAF mutation is called V600E which was previously known as V599E. Prevalence About 5-9% of colorectal cancer tumors have a V600E BRAF mutation.1 Prognosis Patients with a V600E BRAF mutation appear to have a poorer prognosis. Tumors with BRAF mutations may have less response to anti-EGFR therapies like cetuximab (Erbitux® ) and panitumumab (Vectibix® ).1 Test information Introduction Testing for a BRAF mutation may include targeted mutation analysis or sequencing. © eviCore healthcare. All Rights Reserved. 1 of 4 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines v2.0.2019 Available tests The following BRAF tests are available to identify mutations. Note BRAF mutation analysis has several other test applications with different criteria (such as melanoma therapeutic response, Lynch syndrome tumor screening, or Noonan syndrome diagnosis). Ensure you are reviewing the correct use of the test. Targeted mutation analysis Laboratories most commonly test for the BRAF V600E mutation, which accounts for about 90% of activating BRAF mutations.2 Mutation analysis requires relatively little tumor material for testing and has high sensitivity. It is also relatively inexpensive.3,4 BRAF mutation analysis is done on fresh, frozen, or paraffin-embedded tissue from either a primary tumor or metastasis.1,3,4 Some molecular diagnostic laboratories perform BRAF mutation analysis by laboratory-developed methods, while others use FDA-approved test kits. Laboratory-developed tests may vary in the specimen type required, methodology used, mutations tested, sensitivity, and other test- specific data. Sequencing Some laboratories sequence all or part of the BRAF gene, which will find a broader spectrum of mutations than targeted mutation analysis. Laboratories that offer sequencing generally do so for a subset of exons where most BRAF activating mutations have been identified. r Sequence analysis requires more and higher quality tumor material for testing than e targeted mutations. This method is typically less efficient and more expensive than c 3-5 targeted mutation analysis. n a C Guidelines and evidence l a Introduction t c This section includes relevant guidelines and evidence pertaining to BRAF testing for e colorectal cancer. r o National Comprehensive Cancer Network l o The National Comprehensive Cancer Network (NCCN, 2018) states the following.1 C - “Limited data from unplanned retrospective subset analyses of patients with metastatic colorectal cancer treated in the first-line setting suggest that although BRAF V600E F mutation confers a poor prognosis regardless of treatment, patients with disease A characterized by this mutation may receive some benefit from the addition of cetuximab to front-line therapy.” R B © eviCore healthcare. All Rights Reserved. 2 of 4 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines v2.0.2019 “Overall, the panel believes that evidence increasingly suggests that BRAF V600E mutation makes response to panitumumab or cetuximab, as single agents or in combination with cytotoxic chemotherapy, highly unlikely. The panel recommends BRAF genotyping of tumor tissue (either primary tumor or metastasis) at diagnosis of stage VI disease.” “Despite uncertainty over its role as a predictive marker, it is clear that mutations in BRAF are a strong prognostic marker.” “Although BRAF genotyping can be considered for patients with tumors characterized by the wild-type KRAS/NRAS genes, this testing is currently optional and not a necessary part of deciding whether to use anti-EGFR agents.” “The panel strongly recommends genotyping of tumor tissue (either primary tumor or metastasis) in all patients with metastatic colorectal cancer for RAS (KRAS exon 2 or non-exon 2; NRAS) and BRAF at diagnosis of stage IV disease.” “Testing for KRAS, NRAS, and BRAF mutations should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualifies to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization).” Criteria Testing may be considered in individuals who meet the following criteria: Individual has been diagnosed with stage IV, metastatic colorectal cancer, AND r BRAF mutation testing is needed for prognostic purposes. e c The following BRAF mutation testing application is considered investigational and n experimental: a C BRAF mutation testing for the purpose of decision making regarding the use of anti- EGFR agents. l a t c References e r Introduction o l These references are cited in this guideline. o C 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in - Oncology: Colon Cancer. Version 2.2018. Available at http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf. F A R B © eviCore healthcare. All Rights Reserved. 3 of 4 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com Lab Management Guidelines v2.0.2019 2. Pichler M, Balic M, Stadelmeyer E, et al. Evaluation of high-resolution melting analysis as a diagnostic tool to detect the BRAF V600E mutation in colorectal tumors. JMD. 2009; 11(2):140-7. 3. Jakubauskas A, Griskevicius L. KRAS and BRAF mutational status analysis from formalin-fixed, paraffin-embedded tissues using multiplex polymerase chain reaction-based assay. Arch Pathol Lab Med. 2010; 134:620-4. 4. Packham D, Ward RL, Lin VA, et al. Implementation of novel pyrosequencing assays to screen for common mutations of BRAF and KRAS in a cohort of sporadic colorectal cancers. Diagn Mol Pathol. 2009; 18(2):62-71. 5. Fakih M. KRAS mutation screening in colorectal cancer: From paper to practice. Clin Colorectal Cancer. 2010;9(1):22-30. r e c n a C l a t c e r o l o C - F A R B © eviCore healthcare. All Rights Reserved. 4 of 4 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com .
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