Now, many guidelines recommend the use of broad molecular profiling, which include tests that evaluate a large number of genes or gene products simultaneously. These tests can encompass genes that were previously evaluated in a single, targeted test, as well as multiple other genes (and sometimes noncoding regions) of potential interest.
One reason that this approach is becoming increasingly popular is that there are now newer drugs or clinical trials available for patients with tumors that harbor rare mutations.1 For example, in 2018, the US Food and Drug Administration (FDA) approved the TRK inhibitor larotrectinib for the treatment of any unresectable or metastatic solid tumor harboring an NTRK alteration, which is a type of mutation called a gene fusion. Although a fusion in this gene is rare in most cancer types, when the mutation is present, larotrectinib appears to offer a highly effective treatment option.
Insurance coverage of broad molecular profiling tests varies by insurance company and cancer type. According to a 2018 analysis, coverage of sequencing of a patient’s genome by Medicare is more common in NSCLC, colorectal cancer (CRC), myeloproliferative disease, and myelogenous leukemia.6
Medicare now covers broad molecular profiling as next-generation sequencing for patients with recurrent, relapsed, or refractory stage III or stage IV cancer using a test that is FDA approved and that is used for the indication for which it was approved.9 Although this policy will ensure that patients who undergo the type of genomic testing that falls within these strict criteria will have coverage, it does not guarantee that all broad molecular profiling tests will be reimbursed.
The 2 broad molecular profiling next-generation sequencing tests approved by the FDA that interrogate the most number of genes at once are the the FoundationOne CDx (F1CDx) test and the MSK-IMPACT test.10-11 The CMS fee for the FoundationOne CDx assay, which surveys 324 genes and is represented by CPT code 0037U, was listed as $3500 in 2019. The CMS fee paid for MSK-IMPACT, which offers analysis of 468 cancer-associated genes and is represented by code 0048U, was listed as $0 (although MSK-IMPACT is an assay that is approved by the FDA, it is not yet covered by Medicare, as it is not considered a companion diagnostic). There are also several other next-generation sequencing tests that are approved by the FDA that target a specific gene or several genes.12-14
- El-Deiry WS, Goldberg RM, Lenz H-J, et al. The current state of molecular testing in the treatment of patients with solid tumors, 2019. CA Cancer J Clin. doi: 10.3322/caac.21560
- McKenzie AJ, Dilks HH, Jones SF, Burris H III. Should next-generation sequencing tests be performed on all cancer patients? Exp Rev Mol Diagn. 2019;19(2):89-93.
- Ettinger DS, Wood DE, Aggarwal C, et al. Non-Small Cell Lung Cancer, Version 4.2019. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. April 29, 2019.
- Motzer RJ, Jonasch E, Agarwal N, et al. Kidney Cancer, Version 4.2019. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. April 25, 2019.
- Centers for Medicare and Medicaid Services. Clinical laboratory fee schedule. Updated February 27, 2019. Accessed June 14, 2019.
- Lu CY, Loomer S, Ceccarelli R, et al. Insurance coverage policies for pharmacogenomic and multi-gene testing for cancer. J Pers Med. 2018;8(2):E19.
- Centers for Medicare and Medicaid Services. Clinical laboratory fee schedule; Centers for Medicare and Medicaid Services: Baltimore, MD; 2017.
- Centers for Medicare and Medicaid Services. Clinical laboratory fee schedule; Centers for Medicare and Medicaid Services: Baltimore, MD; 2019.
- CMS. Decision Memo for NEXT GENERATION SEQUENCING (NGS) for Medicare Beneficiaries with Advanced Cancer (CAG-00450N). March 16, 2018.
- US Food and Drug Administration. FoundationOne CDx – P170019. Website. www.fda.gov/medical-devices/recently-approved-devices/foundationone-cdx-p170019. Accessed May 30, 2019.
- Memorial Sloan Kettering Cancer Center. MSK-IMPACT™ is the first tumor-profiling multiplex panel authorized by the FDA, setting a new pathway to market for future oncopanels. Press Release. 2017. www.mskcc.org/press-releases/msk-impact-first-tumor-profiling-multiplex-panel-authorized-fda-setting-new-pathway-market-future-oncopanels. Accessed May 30, 2019.
- ThermoFisher. FDA Approves First Companion Diagnostic Test to Simultaneously Screen for Multiple Non-Small Cell Lung Cancer Therapies. Press Release. 2017. http://thermofisher.mediaroom.com/2017-06-22-FDA-Approves-First-Companion-Diagnostic-Test-to-Simultaneously-Screen-for-Multiple-Non-Small-Cell-Lung-Cancer-Therapies. Accessed May 30, 2019.
- US Food and Drug Administration. FoundationFocus CDxBRCA LOH – P160018/S001. Website. 2018. https://www.fda.gov/medical-devices/recently-approved-devices/foundationfocus-cdxbrca-loh-p160018s001. Accessed May 30, 2019.
- US Food and Drug Administration. FDA granted marketing approval to the Praxis Extended RAS Panel. Website. 2017. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-marketing-approval-praxis-extended-ras-panel. Accessed May 30, 2019.