Impact of Next-Generation Sequencing Tests on Clinical Pathways for Cancer Care

The hallmark of clinical pathways is the adoption of evidence-based practices to ensure quality care for patients. Such pathways bring standardization to patient care, with the goal of improving outcomes while reducing risks in a cost-effective manner. Critical to the success of clinical pathways is the use of high-quality diagnostic tools to inform patient management.

Cancer care is an excellent demonstration of the potential benefit of clinical pathways to both patients and the healthcare system. We are now firmly in the era of targeted cancer treatments and moving toward more frequent use of immunotherapies and even cellular therapies. In this paradigm, therapeutics developers, diagnostic innovators, payers, healthcare providers, and, most important, patients are aligned in their wish to see the adoption of diagnostic tools that can deliver effective and efficient care. With patients living longer thanks to new therapies, we need more accurate, sensitive, and standardized tools to guide their therapy.

Today, companion and complementary diagnostics offer a cost-effective way to help manage and tailor patient care.¹ Next-generation sequencing (NGS) is a powerful technology platform that investigators and clinicians are employing across various cancers to:

• Identify biomarkers that inform treatment decisions
• Detect the presence of disease
• Assess prognosis
• Evaluate depth of response to therapy
• Monitor disease burden over time

NGS tests have already had a significant impact on patient care and demonstrated potential value to the healthcare system, when appropriately used. In a study published in JCO Precision Oncology, investigators used the FoundationOne comprehensive genomic profiling (CGP) test to match patients to targeted therapies based on their tumor’s genetic profile. The study demonstrated that patients who received CGP early in their therapy showed improved outcomes with reduced costs.² This is one of many studies that validate the importance of molecular testing in clinical practice and demonstrate the value of real-world evidence to inform use of target therapies and improve patient outcomes. Cancer centers like Texas Oncology are developing pathways that allow a physician to input the diagnosis and stage of the disease into the tool for testing recommended by National Comprehensive Cancer Network guidelines to tailor treatment based on the patient’s disease.

Some NGS tests may directly assess the extent of underlying disease, which is essential to patient care for hematologic malignancies, as the tests can determine response to treatment, monitor changes in disease burden, and detect early signs of relapse. A key example is the assessment of minimal residual disease (MRD), the small number of cancer cells that can remain after treatment, in hematologic cancers. Although MRD is not a new concept, the recent availability of highly standardized, sensitive, and quantitative assessment methods has dramatically changed the way it is influencing patient management and drug development. Adaptive’s clonoSEQ Assay is the only FDA-cleared diagnostic test for the detection and monitoring of MRD in multiple myeloma and B-cell acute lymphoblastic leukemia (ALL) from bone marrow, and it represents the first commercial application using NGS to directly track tumors.³

Clear examples already exist of how providers are using MRD to facilitate more cost-effective delivery of care:

• Practitioners use assessment of MRD following induction therapy in ALL to determine whether a patient should be a candidate for a novel therapy to further reduce disease, whereas patients who have achieved MRD negativity following induction may proceed to a less intensive, less expensive course of therapy.⁴
• Patients with multiple myeloma who achieve deep and sustained levels of undetectable MRD negativity may potentially discontinue maintenance therapy or move to limited-duration therapy.⁵
• MRD assessment following chimeric antigen receptor (CAR) T-cell therapy can assess response and determine whether long-term outcomes are likely to be favorable or whether additional treatment (ie, transplant) may be needed.⁶

To realize the benefits of molecular diagnostics more broadly, the oncology community must expand patient access and integrate innovative new technologies into clinical practice and therapeutic pathways. Despite the supporting data, challenges remain. Working within the existing system takes considerable time and investment, moving stepwise to validate emerging clinical uses. Expanded access to advanced molecular testing is essential to realize the promise of precision medicine. Advanced technologies are accelerating our ability to develop novel diagnostics, which will continue to address barriers to access now, before the next wave of NGS-based diagnostics are here. This is critical, because the next wave of applications is likely to continue to have a significant impact on outcomes.

As diagnostic technologies continue to improve, assessment and monitoring of cancer at the molecular level is transforming patient care and lowering costs to the system, making precision medicine a reality. For the medical community to realize the potential of NGS-based technologies, payers, diagnostic developers, and therapeutics companies need to work together to develop models that foster and encourage the standardized, guideline-driven use of these tools in clinical pathways. Author Information

Lance Baldo, MD, is chief medical officer of Adaptive Biotechnologies. Before joining Adaptive, Baldo served in various roles of ascending responsibility with the Roche Group and its affiliates from February 2010 to April 2019, including most recently as senior vice president and head of US medical affairs of Genentech. References

1. Chiang AC, Ellis P, Zon R. Perspectives on the use of clinical pathways in oncology care. Am Soc Clin Oncol Educ Book. 2017;37:155-159. doi: 10.14694/EDBK_175533.

2. Chawla A, Janku F, Wheler J, et al. Estimated cost of anticancer therapy directed by comprehensive genomic profiling in a single-center study [published online November 2, 2018]. JCO Precis Oncol. doi: 10.1200/PO.18.00074.

3. clonoSEQ [technical summary]. Seattle, WA: Adaptive Biotechnologies Corp; 2018.

4. Blincyto [package insert]. Thousand Oaks, CA: Amgen; 2019.

5. Anderson KC, Auclair D, Kelloff GJ, et al. The role of minimal residual disease testing in myeloma treatment selection and drug development: current value and future applications. Clin Cancer Res. 2017;23(15):3980-3993. doi: 10.1158/1078-0432.CCR-16-2895.

6. Turtle CJ, Hay KA, Hanafi LA, et al. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol. 2017;35(26):3010-3020. doi: 10.1200/JCO.2017.72.8519.

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