As stakeholders in the healthcare system learn more about the genetic basis of disease and response to therapy, many view precision medicine as an important strategy to optimize diagnosis, treatment, and prevention of many conditions. With a significant number of products coming to market for the treatment of patients with a specific mutation or biomarker, the paradigm is shifting in certain disease states from a one-size-fits-all approach to a more targeted, biomarker-driven one.1

To date, oncology has been one of the largest areas of development for biomarker-directed therapies, with many tumor types being driven by an identified mutation. The availability of biomarker-targeting therapies has revolutionized the treatment of certain tumors, including non-small cell lung cancer (NSCLC), breast cancer, and acute myeloid leukemia (AML) to name a few. Both the use of biomarker-targeted treatments and biomarker testing have been embraced by the National Comprehensive Cancer Network (NCCN), which has also supported coverage of testing and treatments by payers. In addition to biomarkers that are specific to tumor type, there have also been approvals of biomarker-targeted therapies irrespective of tumor type, such as Vitrakvi® (larotrectinib) for neurotrophic receptor tyrosine kinase (NTRK) gene fusion and immuno-oncology drugs for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors.

In certain tumor types, there are recommendations for patents to undergo germline genetic testing, to identify potential inherited mutations that may impact the patient’s risk of developing a certain type of cancer, aid in diagnosis, and/or inform prognosis and treatment options. NCCN has recommendations for when germline testing is appropriate for breast cancer, ovarian cancer, pancreatic cancer, and most recently in prostate cancer. While information such as a patient’s inherited genetic mutations can help personalize their treatment journey, there may be additional implications of the results. It is critical that patients who undergo germline testing do so in collaboration with their oncology treatment team, including a genetic counselor, to ensure that the patient understands the results and their impact.2,3

There are some inherent challenges to the use of companion diagnostics outside oncology. For example, many diseases are polygenic, or resulting from mutations in more than one gene. Additionally, it can often be more difficult to obtain diseased tissue for sampling in non-oncology indications.4 Another area where biomarkers have strong utility is in the rare disease space, where many conditions have a genetic basis, and the use of biomarkers for patient identification has helped to support accelerated approval for many of these products.5

Researchers are employing innovative techniques, including the use of models, digital technology, and artificial intelligence, to identify targetable mutations in oncology and beyond.1 As the understanding of how both somatic and germline mutations evolve, treatment pathways and paradigms will continue to change. Rapid changes in treatment approach can present a challenge for providers, and some may be hesitant to change their practice. It may be particularly challenging when multiple mutation targets exist within a tumor type, or there is a complicated treatment sequence. Payers have become well acquainted with the management of companion diagnostics in oncology and have generally supported testing for patients treated with the respective drug, as long as the use is consistent with the FDA-approved indication and/or NCCN guideline recommendations.

Expansion of the use of genetic testing within oncology and beyond may increase payer scrutiny around the use of genetic testing. Payers will want to understand the value of genetic testing, which includes the actual cost of the test, but also how the results will be used to shape decisions around treatment. While the use of testing panels or next-generation sequencing can help providers to easily obtain the complete information related to a patient’s mutation profile, payers may be leery of the increased cost and overall value, especially if the panel evaluates mutations that are not actionable. This could lead to coverage restrictions or reimbursement issues impacting the patient and provider.

As manufacturers bring additional products to market that require the use of companion diagnostics and/or germline testing, it will be important to position the testing requirement as adding value to the overall treatment process. Payers will need to understand how using the patient’s genetic make-up to guide targeted treatment improves outcomes relative to the current one-size-fits-all approach. Manufacturers should also consider how they can best educate both providers and patients on the appropriate use of genetic testing as part of their treatment process.


  1. Hartl D, de Luca V, Kostikova A, et al. Translational precision medicine: an industry perspective. J Transl Med. 2021;19(1):245.
  2. National Comprehensive Cancer Network. Genetics screening.
  3. Owens K, Schlager L, Welcsh PL. The impact of germline testing for hereditary cancer postdiagnosis. Am J Manag Care. 2019;25(9):SP285-SP287.
  4. Cohen J. Gradual progress in precision non-oncology, but challenges persist. Forbes. Published July 10, 2018.
  5. Kakkis ED. Aduhelm’s accelerated approval offers a promising roadmap for rare neurological diseases. STAT. Published July 7, 2021.