Tumor genomic profiling using the Guardant360 liquid biopsy-based test is as effective as standard-of-care tumor biopsy-based assays in identifying guideline-recommended biomarkers with matched U.S. Food and Drug Administration(FDA)-approved targeted therapies in patients with newly diagnosed advanced non-small cell lung cancer (NSCLC), according to a press announcement on results from the Noninvasive vs. Invasive Lung Evaluation (NILE) trial (ClinicalTrials.gov Identifier: NCT03615443).1

The Guardant360 assay is a commercially available next-generationsequencing test for identifying alterations in 73 genes from cell-free tumor DNA, and is performed on samples of blood plasma.2 In contrast, tumor-based tests, such FoundationOne CDx, a next-generation sequencing assay, often provide the sequences of a larger number of genes (ie, 324 in FoundationOneCDx).3 In addition, traditional tumor-based genotyping assays, which are not next-generation sequencing tests and typically interrogate a more limited number of genes, are frequently used in the setting of advanced NSCLC.1 Nevertheless,tumor-based assays, unlike the Guardant360 assay, require a tumor biopsy and are invasive, which may be particularly important in the management of cancers such as NSCLC which frequently involves multiple assessments of tumor DNA over time as a result of acquired resistance to targeted treatments.

The NILE trial is a multicenter,prospective study involving 282 patients with newly diagnosed, advanced NSCLC. The primary endpoint of the study is the proportion of tumor genomic alterations found in at least 1 of 7 predictive biomarkers (ie, EGFR, ALK, ROS1, BRAF,MET, ERBB2, and RET) recommended for testing in the National Comprehensive Cancer Network (NCCN) Guidelines for NSCLC using the Guardant360 assay compared with standard-of-care tumor-based genotyping assays.1,4 The rationale for inclusion of the 7 predictive biomarkers in the NCCN NSCLC guidelines is that identification of alterations in these genes can guide treatment decisions related to use of targeted therapy for up to 30% of patients.1,4

Results of the NILE trial showed that mutations in at least 1 of the 7 guideline-recommended predictive biomarkers were identified in 77 and 60 patients tested using the Guardant360 assay and a traditional tissue-based genotyping assay, respectively(P <.0001). Of note, some of the tumor biopsy specimens were not suitable for testing. Although 12 of the 60 patients had an identified predictive biomarker in tumor alone (not seen with the Guardant360 assay), the number of patients with an identified predictive biomarker increased by 48% when the Guardant360 assay was performed in addition to tumor-based genotyping. Furthermore, in the specimens that were negative fora predictive biomarker by a tumor-based assay, addition of the Guardant360 assay increased the number of patients with an identified KRAS mutation, a prognostic biomarker, from 24 to 92.1

Importantly, a comparison of the alterations obtained with the 2 types of assays regarding mutations in 4 predictive biomarkers (EGFR, ALK, ROS1,and BRAF) for which there are FDA-approved targeted therapies, showed concordant results, with a positive predictive value of 100%. Of note, the median time to results was shorter using the Guardant 360 assay compared with the tumor-based assays (9 days vs 15 days,respectively; P <.0001).

The results of the NILE trial will be presented at the American Association for Cancer Research (AACR) Annual Meeting in Atlanta, Georgia, on April 2, 2019.


  1. Liquid Biopsy-based Test As Good As Tissue-based Test for Identifying Treatment for Lung Cancer [news release]. Philadelphia, PA: American Association for Cancer Research; February 27, 2019.https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1271.Accessed February 27, 2019.
  2. Guardant. https://guardanthealth.com/solutions/.Accessed February 26, 2019.  
  3. FoundationOne CDx. FoundationOne CDxTechnical Information. https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170019C.pdf. Accessed February 26, 2019.
  4. National Comprehensive Cancer Network(NCCN) Non-Small Cell Lung Cancer Guidelines. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Updated January 18, 2019. Accessed February 26, 2019.