The cumulative time-to-test results and initiating treatment in the model (which included test processing time and time for re-biopsy) was 2 weeks for upfront NGS and hotspot panel testing compared with 4.7 weeks to 4.8 weeks for sequential testing with or without KRAS testing — upfront testing was 2.7 weeks to 2.8 weeks faster.1 Upfront NGS resulted in cost savings exceeding $1.5 million compared to sequential individual-gene testing for a hypothetical population of 2066 Medicare-insured patients, based on the Centers for Medicare & Medicaid Services (CMS) reimbursement rates — and savings of more than $2.1 million compared with hotspot panel testing.1 NGS was also the least-expensive testing strategy in the authors’ commercial-insurer model.1

But assessing the economic value of NGS is a major challenge with no easy solutions, cautioned Kathryn A. Phillips, PhD, of the University of California, San Francisco (UCSF) Institute for Health Policy Studies and the UCSF Comprehensive Cancer Center, who is also the founding director of the UCSF Center for Translational and Policy Research on Personalized Medicine (TRANSPERS).3 Each approach has its own set of advantages and shortcomings, so much more work is needed.

It is important to note that the authors conducted a budget impact analysis, not a cost-effectiveness analysis, Dr Phillips told Cancer Therapy Advisor.

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“The former is not used as frequently and it doesn’t answer the same questions,” Dr Phillips explained. “However, I have often noted that budget impact analysis can be very useful for these types of questions and thus, it’s good to have more evidence to add to what is known.”

Among 282 patients with previously untreated mNSCLC in the separate, prospective “non-invasive versus invasive lung evaluation (NILE) ” study ( Identifier: NCT03615443), researchers found that comprehensive circulating cell-free tumor DNA (cfDNA; Guardant360) identified guideline-recommended biomarkers significantly more frequently than did conventional tissue genotyping (77 patients vs 60 patients, or 27% vs 21%; noninferiority P <.0001).4

“A comprehensive approach such as comprehensive NGS can minimize tissue wastage and turnaround time for patients,” said study author Natasha B. Leighl, PhD, Princess Margaret Cancer Centre, the University of Toronto, Ontario, Canada. “Turnaround time is also critical, as patients with metastatic NSCLC are often diagnosed late and have limited time to access treatment before they become too unwell for treatment. cfDNA helps us to identify genomic biomarkers in a majority of patients in a short period of time and helps us increase the chance of getting complete genotyping on our patients in time to help them access precision therapy.”

Along with tissue genotyping, Dr Leighl and colleagues have been able to identify actionable targets in more patients than with either method alone, she told Cancer Therapy Advisor

“We’ve made tremendous progress in bringing the reality of precision medicine to patients with metastatic NSCLC,” Dr Leighl said. “The first step is to identify actionable targets, of which there are at least 10 — 9 of which are genomic targets.”

An enduring challenge with mNSCLC is obtaining sufficient tissue for complete genotyping, Dr Leighl said. 

“Up to 15% to 40% of our metastatic NSCLC patients do not have enough tissue for testing — and repeat biopsy may be required,” she said. “As the number of relevant markers increases, tissue requirements for serial testing also increase. In the NILE study, we found that only 18% of patients had complete biomarker testing — and only 5.6% were able to have serial testing for all recommended markers.”

The clinical application of cfDNA in NSCLC has “tremendous potential,” Dr Leighl added.

“Evidence to support its utility in the detection of targeted therapy resistance, diagnosis, disease monitoring, and now, early detection is rapidly growing,” she explained. “In Canada, we have developed several studies to demonstrate the value of cfDNA testing in detection of resistance, as well as diagnosis in our patients with metastatic NSCLC in conjunction with standard biopsy and tissue testing.”


  1. Pennell NA, Mutebi A, Zhou ZY, et al. 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 [published online May 16, 2019]. JCO Precis Oncol. doi: 2810.1200/PO.18.00356
  2. Leighl NB, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer [published online April 15, 2019]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-19-0624
  3. Yu TM, Morrison C, Gold EJ, Tradonsky A, Arnold RJG. Budget impact of next-generation sequencing for molecular assessment of advanced non-small cell lung cancer. Value Health. 2018;21(11):1278-1285.
  4. Phillips KA, Deverka PA, Marshall DA, et al. Methodological issues in assessing the economic value of next-generation sequencing tests: many challenges and not enough solutions. Value Health. 2018;21(9):1033-1042.