Upfront Next-Generation Sequencing Is Faster, More Cost-Effective in Metastatic NSCLC

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The researchers argue that upfront next-generation sequencing should be the new standard of care.
The researchers argue that upfront next-generation sequencing should be the new standard of care.

Use of upfront next-generation sequencing (NGS) to test for lung cancer-related gene changes at the time of diagnosis was more cost-effective and faster than testing for a single gene or a limited number of genes at a time, according to the results of a study that compared different types of genetic testing in metastatic non-small cell lung cancer (NSCLC).1

“Every patient with advanced or metastatic non-squamous non-small cell lung cancer should undergo genetic biomarker testing to guide treatment, and I believe that using NGS is the fastest and most cost-efficient way to do that testing,” said Nathan A. Pennell, MD, PhD, co-director of the Cleveland Clinic Lung Cancer Program in Ohio who presented the results of this study at a press conference ahead of the 2018 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

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Several genes are known to be altered in NSCLC including MET, HER2, RET, and NTRK1, and some genes, such as EGFR, ALK, ROS1, and BRAF are actionable. As part of their research, Dr Pennell and colleagues created a decision analytic model for patients with newly diagnosed metastatic NSCLC to determine which gene testing approach was the most cost effective and efficient.

In the study, patients underwent NGS with either sequential tests (one gene at a time), exclusionary mutation testing for KRAS followed by sequential tests if KRAS was not mutated, a panel test looking for EGFR, ALK, ROS1 and BRAF, or upfront NGS.

Using estimates of the number and age of people with metastatic NSCLC in the United States each year, the researchers estimated that for 1 million-member health plans, 2066 tests would be paid for under CMS and 156 would be paid for by commercial insurers. The model also incorporated time to receive results and total cost for test and any necessary rebiopsy.

In this hypothetical model, estimated time to receive results was 2 weeks for NGS and panel testing; this was 2.7 and 2.8 weeks faster than exclusionary KRAS testing and sequential testing, respectively.

Using CMS reimbursement, NGS resulted in a savings of almost $1.4 million compared with exclusionary testing, $1.5 million compared with sequential testing, and more than $2.1 million compared with panel testing. For commercial payers, NGS was the least expensive as well by almost $4,000 compared with exclusionary testing and more than $250,000 compared with panel testing.

“NGS at the time of diagnosis to check for actionable genetic changes in patients with advanced NSCLC is the most time-, tissue-, and cost-efficient way to do molecular testing,” Dr Pennell told Cancer Therapy Advisor. “NGS simply provides the best value compared to the alternatives.”

According to Dr Pennell, upfront NGS should be the standard of care “instead of single gene tests everywhere” and “payers should be willing to cover NGS testing because it's the right thing for patients and for the health system as a whole.”

He also noted that “patients will squamous cell carcinoma don't usually need to have this done unless there are scenarios such as being young ― under age 50 ― or being never or very light smokers.”


  1. Pennell NA, Mutebi A,  Zhou Z-Y, et al. Economic impact of next generation sequencing vs sequential single-gene testing modalities to detect genomic alterations in metastatic non-small cell lung cancer using a decision analytic model. J Clin Oncol. 2018;36:(suppl; abstr 9031).

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