The number of guideline-recommended biomarkers to be assessed in patients with newly diagnosed, metastatic non–small cell lung cancer (NSCLC) is increasing. These biomarkers include both predictive targets—including EGFR, ALK, ROS1, BRAF, RET, MET, and ERBB2—and prognostic markers, such as KRAS. A prospective study comparing Guardant360, a cell-free DNA (cfDNA) liquid biopsy test, with standard-of-care tissue genotyping to identify guideline-recommended genomic biomarkers in patients with advanced NSCLC has found that the cfDNA test detects Guideline-7 (G7) biomarkers at a rate similar to tissue genotyping tests. The cfDNA test also had a significantly faster turnaround time from test order to final results: 9 days vs 15 days, respectively. The study results demonstrate the clinical utility of cfDNA in newly diagnosed patients with metastatic NSCLC, according to the study authors. The study by Leighl et al was presented at a presscast in advance of the American Association for Cancer Research (AACR) Annual Meeting 2019 (Abstract 4460).
The researchers launched a prospective, multicenter study called Noninvasive vs Invasive Lung Evaluation (NILE) to demonstrate the noninferiority of comprehensive cfDNA relative to standard-of-care tissue genotyping to identify guideline-recommended genomic biomarkers in patients with metastatic NSCLC. Between July 2016 and April 2018, the researchers enrolled 282 newly diagnosed patients with previously untreated, nonsquamous, metastatic NSCLC undergoing standard-of-care tissue genotyping.
Patients submitted a pretreatment blood sample for cfDNA analysis utilizing a clinical laboratory improvement amendments–certified, comprehensive 73-gene next-generation sequencing panel (Guardant360). Turnaround time was defined as time from test order to final results.
A G7 biomarker was identified in the tissue of 60 patients and by cfDNA in 77 patients (21.3% vs 27.3%; P < .0001). In the 60 tissue-positive patients, the biomarker was identified in tissue alone (12) or concordant with plasma (48). Utilizing cfDNA increased the number of patients with an identified G7 biomarker by 48%—from 60 patients to 89—including those with negative (7), not assessed (16), or quantity not sufficient (QNS, 6) results in tissue. Of the 193 patients without a G7 biomarker by tissue or cfDNA, 24 (12.4%) had an activating KRAS alteration identified in tissue alone (3) or concordant with cfDNA (21). cfDNA increased the number of KRAS-positive patients from 24 to 92 (tissue-negative = 3; not assessed = 60; QNS = 5). Positive predictive value for cfDNA vs tissue genotyping for FDA-approved targets
(EGFR, ALK, ROS1, BRAF) was 100%. Median turnaround time was significantly lower for cfDNA compared to tissue genotyping (9 vs 15 days; P < .0001).
Limitations of this study included that the liquid biopsy test was compared to a current standard-of-care tissue genotyping test and not the tissue-based next-generation sequencing test, and that the study results are only applicable to the Guardant360 test and not to other liquid biopsy tests.
“The findings in this prospective, multicenter North American study confirm similar findings in Europe and add to the growing evidence that cfDNA can be successfully used to completely assess and identify G7 biomarkers significantly faster than tissue testing, can rescue G7-positive patients with nondiagnostic tissue results, and demonstrates the clinical utility of cfDNA in newly diagnosed metastatic NSCLC,” concluded the study authors.
“The results of this study are exciting and reveal several important things,” commented John D. Carpten, PhD, Program Chair of the AACR Annual Meeting, the presscast. “One is that noninvasive approaches are feasible and they meet standards that are minimally at the level of, if not superior to, more invasive approaches to disease detection, such as … genotyping from actual tissue specimens, which would require either a biopsy or surgical resection. In this case, we can actually identify the cancer, identify the mutations in the cancer that are really important, and do this in a much more noninvasive way. This also reveals that this field is growing incredibly rapidly with a new method that might also include measuring epigenetic changes in cell-free DNA, circulating tumor cells and exosomes, and other forms of mRNA that might be circulating in plasma. The integration of all these various measurements, we believe, will really allow us to do a much better job at identifying cancers, monitoring them, and identifying appropriate mutations or alterations that are tied to very specific targeted therapies.”
Disclosure: This study was funded by Guardant Health. The study authors' full disclosures can be found at abstractsonline.com.
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