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Specificity in NSCLC Treatment Grows With Acceptance of NGS and cfDNA

Angelica Welch
Published: Wednesday, Nov 21, 2018

Dr. Benjamin P. Levy
Benjamin P. Levy, MD
The introduction of next-generation sequencing (NGS) platforms and cell-free DNA (cfDNA) have provided the opportunity for clinicians to be more specific in targeting mutations in patients with non–small cell lung cancer (NSCLC), according to Benjamin P. Levy, MD.

abnormalities. This list of targets answers the question of why genomic testing should be done in patients with NSCLC, according to Levy. This goes beyond lung cancer, he added, as basket trials such as ASCO’s TAPUR study and the NCI-MATCH trial include patients from multiple tumor types.

Questions on Implementing Sequencing

A recently published study in JAMA on advanced NSCLC sought to determine the association of broad-based genomic sequencing and survival in the community oncology setting.1 This study looked at the difference between patients who had comprehensive genomic profiling of their lung cancer versus those who had only had EGFR and ALK panel testing. This retrospective analysis of over 5000 patients showed no difference in outcomes, and broad-based genomic sequencing only directly informed treatment in a minority of patients. This was a surprising result, Levy explained.

"NGS was cost effective when compared with sequential, exclusionary, and a hotspot panel, both for a CMS and Medicare perspective, and for commercial payers. This is a hypothetical patient population, but there is a lot more work we need to do to understand whether this is cost effective or not," summarized Levy.

Liquid Biopsies

Although NGS is a beneficial option, Levy noted that the turnaround time is often long. There are also issues with tissue procurement. Traditional tissue biopsies are invasive, and there are questions regarding tissue stewardship. Additionally, every institution has a different way of reporting results from the tissue biopsy, Levy said.

"Where does the tissue go? You do the biopsy, it is sent to the pathology lab, then it goes to a whole different bunch of labs," Levy explained. "How do we find the tissue? Where is it? Once it is pinned down, how do you report it? There are challenges with tissue, even in the best of circumstances."

cfDNA is captured by a simple noninvasive blood test, often referred to as a liquid biopsy. Shedding of cfDNA is a product of apoptosis and necrosis, and now more sensitive diagnostic platforms have the capability to genetically interrogate isolate DNA from the blood, explained Levy. This method may circumvent the need for tissue biopsies, he added.

The FLAURA trial of osimertinib (Tagrisso) established the agent as the new standard of care for patients with NSCLC who have EGFR sensitizing mutations. Investigators on this trial showed that there was a concordance between plasma and tumor tissue testing by EGFR mutation status. High sensitivity was observed for those with exon 19 deletions and exon 21 L858R substitution mutations, noted Levy.

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Archived Version of a Live Webcast: Virtual Current Trends™: European Perspectives on the Advancing Role of CAR T-Cell Therapy in Hematologic MalignanciesJun 29, 20192.0
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