Does Every Cancer Patient Get Next Generation Sequencing?

Summary in Thirty Seconds

• Next Generation Sequencing (NGS) can identify multiple genetic variants in a single test and can be used not only for diagnosis and prognosis but also for targeted therapy treatment decisions and monitoring of resistance; however, NGS is still not consistently used by oncologists.

• Nearly 80% of patients with cancer have potentially actionable genomic alterations; thus, NGS testing is likely valuable for all patients with advanced cancer.

• NGS testing adoption rates have increased in the past ten years, yet, despite the importance of NGS testing, many cancer patients are still not getting guideline-indicated biomarker testing of their tumors.

• Improving awareness amongst healthcare providers and patients of the value of biomarker testing is one straightforward way to increase the use of NGS testing in cancer.

Next Generation Sequencing Uses

Precision medicine has altered treatment approaches for people with cancer with an ever-increasing number of biomarkers identified across an array of cancer types. Genomic test data is used in making treatment decisions with greater frequency, and such data has become more feasible as the “affordability, accessibility, and reliability…of sequencing platforms and bioinformatics capabilities enable oncologists to provide more personalized care.”[1] Next Generation Sequencing (NGS) can be used not only for diagnosis and prognosis but also for treatment decisions and monitoring of resistance.[2] However, NGS is still not consistently used by oncologists. An ASCO survey[3] of over 1,000 oncologists found that 75.6% reported using NGS in the past year, with higher usage among those who were under 50 years of age, had a faculty appointment, had genomic training, were part of a practice with a molecular tumor board, or who treated fewer than 50 patients with cancer per month. Thirty-four percent of oncologists used NGS testing to guide treatment decisions for patients with advanced refractory disease. Twenty-eight percent of surveyed oncologists reported using NGS testing when treating patients with rare cancers, and 21% used NGS testing for patients with an initial diagnosis of cancer.

These survey results contrast with a JAMA Oncology study[4] showing that nearly 80% of patients with cancer had potentially actionable genomic alterations, and of those who received sequencing-directed therapy, nearly 40% received some clinical benefit, while approximately 20% experienced exceptional responses (progression-free survival for at least one year). Furthermore, McKenzie et al. argue that NGS testing should be used for all patients with advanced cancer.[5] Yet, this is still not the case. An example from non-small cell lung cancer (NSCLC) is telling.

NGS in NSCLC

A study presented at ASCO 2022[6] evaluated the use of NGS between 2010 and 2018 in almost 38,000 patients with stage IV NSCLC. Approximately 22% of all NSCLC patients had molecular testing, and specifically in those with adenocarcinoma, the rate was 49%. Unsurprisingly, those patients who had NGS performed on their tumors were more likely to have been treated with immunotherapy and targeted therapy. The study concluded that “The percentage of patients undergoing testing remains sub-optimal,” given that NSCLC adenocarcinoma has possibly the strongest reason for routine NGS use given the high degree of mutation burden and a high number of driver mutations.[7] ESMO echoes ASCO, recommending “routine use” of NGS for non-squamous cell NSCLC, (as well as for prostate and ovarian cancers and cholangiocarcinoma).[8]

NGS Progress

NGS testing adoption rates have increased in the past ten years, with rates for advanced NSCLC, metastatic colorectal cancer, metastatic breast cancer, and advanced melanoma increasing from less than 1% in 2011 to approximately 40% in 2019.[9]

There are many reasons for this increase, most notably due to additional research on mutation drivers, the efficacy of NGS, and the development of targeted treatments.[10] Along with research and development advancements, a practical contributor to the rise in NGS utilization is the decision by the Centers for Medicare & Medicaid Services to cover initial and further NGS testing for all solid tumors with a companion diagnostic claim.[11] However, there are still substantial gaps in insurance coverage. A survey of more than 3,000 patients in 2020 with cancer revealed that about 1 in 8 patients with cancer reported NGS testing was still not covered by their insurer.[12]

A Growing Need with Notable Benefits

NGS testing can identify multiple genetic variants in a single test, allowing for one specimen to be tested for hundreds of genetic alterations. The clinical and economic benefit of NGS is increasing as more targets are identified and more targeted therapies are approved.[13] A clear example of this has been the evolution of tumor-agnostic therapies (e.g., entrectinib and larotrectinib), providing treatment for molecular alterations regardless of the cancer origin.[14][15]A recent study by Pennell et al.[16] stated that “if all patients identified with specific actionable driver mutations (EGFR, ALK, ROS1, BRAF, RET, MET, and NTRK) were assumed to receive matched treatment, it would result in substantial gain in life years at a reduced cost.” Yet, despite the value and importance of NGS testing, many cancer patients are still not getting guideline-indicated biomarker testing of their tumors.

Solutions

The studies cited above show that while NGS use is increasing there are still large areas in which it is not being used, even in cancer types where there are unquestionable benefits from its use. Such shortfalls are seen not just in diagnostic decision-making but also in treatment matching and resistance monitoring. Improving the use of NGS testing in cancer will likely take a multi-pronged approach. While many insurance carriers now provide coverage (to some degree) for NGS testing, there are still shortfalls that require addressing. Research continues to uncover more driver mutations that are potentially actionable, and new targeted therapies continue to be developed. Additional research on the implementation and comparative benefits of NGS testing is needed.[17] Such studies would better inform decisions about NGS use. The American Cancer Society lists several recommendations for improving access to biomarker testing,[18] including a variety of patient, provider, and institutional suggestions. Improving awareness amongst healthcare providers and patients of the value of biomarker testing is another potentially fruitful avenue to increasing the use of NGS testing in cancer. With such concerted, multi-faceted efforts, this life-changing and life-saving diagnostic tool can be consistently implemented.

[1] N Engl J Med. 2015; 372:793-795 [2] Curr Oncol. 2019, April;26(2):e241-e254 [3] JCO Prec. Oncol. 2018; 2:1-13 [4] JAMA Oncol. 2021; 7(4):525-533 [5] Expert Rev Mol Diagn. 2019; 19:89-93 [6] J of Clinic Oncol. 2020; 40(16_suppl):9128 [7] Nature 2013; 500:415–421 [8] Ann. of Onc. 2020; 31(11):1491-1505 [9] JCO Oncol Pract. 2021;17(11):e1774-e1784 [10] ibid [11] https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=372 [12] biomarker_one_pager_7.22.20.pdf (fightcancer.org) [13] JCO Oncol Pract. 2021;17(11):e1774-e1784 [14] Lancet Oncol. 2020;21(2):261-270 [15] Lancet Oncol. 2020; 21(4):531-540 [16] J Clin Oncol 38, 2020 (suppl): abstr 9529 [17] BMJ Global Health 2021;6:e004415 [18] Improving Access to Biomarker Testing | American Cancer Society Cancer Action Network (fightcancer.org)