Breaking Down Barriers Preventing the Use of NGS in Cancer Diagnosis and Treatment | Takeda Oncology │ Leadership │ Article

The decisions that a health care provider (HCP) makes immediately after a patient’s cancer diagnosis often define their treatment journey. For patients with lung cancer, one of those critical decisions is when and how to approach diagnostic testing to ensure any cancer-driving mutation(s) are properly identified. Having this information confirmed from the start allows HCPs to prescribe treatment(s) that specifically target their patient’s disease, giving them the best possible chance to optimize outcomes.¹

Next-generation sequencing, or NGS, provides comprehensive testing – helping to optimize diagnosis and ensure HCPs consider all potential treatment options for their patients, including any targeted options that may be available. In rare lung cancers – like epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive (insertion+) non-small cell lung cancer (NSCLC) – NGS testing is a useful tool due to the distinct nature of the mutations.²

So why is this critical tool – one that has improved our understanding of cancer development and progression – not being utilized universally as standard of care?³

We gathered perspectives from experts on what is preventing the universal adoption of NGS, and how these barriers need to be broken down to help HCPs make their care approach stronger and, ultimately, improve outcomes for patients.

It’s important to acknowledge that not all forms of testing are created equal. Due to the heterogeneity in length and positions of certain mutations, NGS is a more comprehensive option for detecting compared to polymerase chain reaction, or PCR, testing, which doesn’t have the same capabilities.^2,4 For example, PCR testing is projected to capture about 50% of EGFR Exon20 insertion+ cases.⁵ Due to its limited ability to identify certain mutations, PCR tests may prevent patients from being prescribed appropriate treatments designed for their specific cancer, potentially preventing them from achieving their desired health outcomes.^2,6

Wider adoption of NGS testing has enabled the identification of rare mutations that may be missed with commercially available tests, leading to a growing number of previously unidentified mutations. This has, in turn, facilitated the use of precision medicine.^7-8 Despite these benefits and capabilities to pinpoint a patient’s lung cancer, NGS testing continues to be underutilized in the clinical setting.⁹ According to a JCO Precision Oncology study that evaluated patients with newly diagnosed advanced NSCLC, approximately 64% of potentially eligible patients for precision oncology therapies appropriate for their lung cancer did not benefit from them due to factors associated with clinical gaps, including pre-analytic biomarker testing.9 Too few clinicians are aware of the potential impact of NGS testing, and broader awareness is needed to ensure lung cancer patients are able to benefit from it.⁹

One of the common concerns from those who are aware of NGS tests is that results take longer than PCR tests, thus pushing back the timeline for when patients can begin treatment.³

While time is of the essence when diagnosing a disease as serious as lung cancer, waiting for the results of the NGS test will ultimately benefit the patient.^3,10 HCPs should look at this issue comprehensively and recognize that prescribing the wrong therapy can cause a negative ripple effect and impact several aspects of the patient’s journey.⁹ Prescribing the wrong treatment may result in the patient’s cancer progressing more quickly or acquiring resistance mutations that complicate treatment sequencing.^9,11-12 When NGS testing is taken into consideration at the very beginning, HCPs can ensure that all potential diagnoses and treatment options are initially explored, facilitating a path for patients to receive an optimized diagnosis and timely treatment decisions.^1,9

PCR tests are the more commonly used testing method because equipment to run them is more accessible and are generally perceived as more cost-effective.^3,11 However, in recent years payers have grown increasingly receptive to reimbursing for NGS tests. There are several ways coverage can be achieved for NGS testing.¹³ Local coverage determination, in which a Medicare Administrative Contractor reviews a test performed in that jurisdiction.

• National coverage determination, which provides access to testing for all Medicare patients nationally.

• Through private payers, which each generate their own coverage policy. Coverage policies from payers can vary significantly and may address all NGS-based tests or just one specific diagnostic test.

• Through Medicaid, in which oncology and biomarker tests are paid for directly on a state-by-state basis through diagnostic companies or health insurance.

The most influential factor on coverage and reimbursement decisions is the clinical evidence that supports the validity of the test. As the reimbursement outlook improves and more targeted therapies are approved, pathologists anticipate an increase in NGS-based testing moving forward.¹³

Using NGS testing provides patients with an optimized diagnosis and thus the opportunity to receive a treatment designed to target their disease at the molecular level.1 This is why Takeda partners with industry stakeholders and companies like Thermo Fisher Scientific, in order to address the urgent need for broader access to genomic tests, ultimately expanding treatment options for patients. Takeda remains dedicated to supporting these efforts to expand the availability and accessibility of NGS testing so that more patients can benefit from and have access to life-transforming medicine.

1. Pennell N et al. JCO Precision Oncology. Economic Impact of Next-Generation Sequencing Versus Single-Gene Testing to Detect Genomic Alterations in Metastatic Non-Small-Cell Lung Cancer Using a Decision Analytic Model. 2019.

2. Viteri S, Minchom A, Bazhenova L, et al. Molecular Oncology. Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real-world genomic datasets. 2022;1:1-8

3. Berger et al. Nat Rev Clin Oncol. The emerging clinical relevance of genomics in cancer medicine. 2018; 15(6):353-365

4. Khoo C, et al. Transl Lung Cancer Res. Molecular methods for somatic mutation testing in lung adenocarcinoma: EGFR and beyond. 2015;4:126-141

5. Ou S, Hong J, Lin H, et al. Journal of Thoracic Oncology. Distribution and Detectability of EGFR Exon20 Insertion Variants in Non-Small Cell Lung Cancer. 2021;16:S928-S929

6. Lin HM et al. Journal of Thoracic Oncology EGFR Testing Patterns and Detection of EGFR Exon 20 Insertions in the United States. 2022;3.

7. Food and Drug Administration. Precision Medicine. 2018. https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine

8. Russo A, et al. Oncotarget. Heterogeneous Responses to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in Patients with Uncommon EGFR Mutations: New Insights and Future Perspectives in this Complex Clinical Scenario. 2015;6:26814-26825.

9. Sadik H, Pritchard D, Keeling DM, et al. JCO Precision Oncology. Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer. 2022;6.

10. Cainao C et al. Biology (Basel). Next Generation Sequencing Technology in Lung Cancer Diagnosis. 2021; 10(9)

11. Schluckebier L, Caetano R, Garay OU, et al. National Library of Medicine. BMC Cancer. Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients. 2020.

12. Pacini L et al. Pharmcogenomics and Personalized Medicine. Tackling Drug Resistance in EGFR Exon 20 Insertion Mutant Lung Cancer. 2021;14:1-17.

13. Ferrara et al. Pieran Dx. 2020 NGS Testing Reimbursement Overview Strategies for Clinical NGS Deck. 2019.

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