Study Confirms Utility of Liquid Biopsies for Biomarker Detection in NSCLC

Guardant360—a 73-gene next-generation sequencing panel—detected all of the guideline-recommended biomarkers in patients newly diagnosed with metastatic non–small cell lung cancer at a similar rate, but in a faster turnaround time than tissue genotyping, according to data from the NILE study.

Vassiliki A. Papadimitrakopoulou, MD

Guardant360—a 73-gene next-generation sequencing panel—detected all of the guideline-recommended biomarkers in patients newly diagnosed with metastatic non—small cell lung cancer (NSCLC) at a similar rate, but in a faster turnaround time than tissue genotyping, according to data from the Noninvasive versus Invasive Lung Evaluation (NILE) study.

According to findings from the study presented during a media preview of the 2019 AACR Annual Meeting 2019, the test also increased the rate of biomarker detection by 48%, from 60 patients identified with at least 1 guideline-recommended biomarker using tissue-based tests alone to 77 patients with the liquid biopsy (21.3% versus 27.3%;P<.0001). This included patients whose samples were negative by tissue (n = 7), not tested (n = 16), or did not have enough material (n = 6) for the tissue-based tests.

“Liquid biopsies can identify these mutations in a safe way with quick turnaround for treatment selection,” study investigator Vassiliki Papadimitrakopoulou, MD, professor of medicine, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center in Houston, said in an interview withTargeted Oncologyahead of the presscast. “… (our study) provides reassurance to physicians with the validity of these results.”

Of the 193 patients without a guideline-recommended biomarker by tissue or liquid biopsy, 24 (12.4%) had an activatingKRASalteration identified in tissue alone (n = 3) or concordant with cell-free (cf) DNA (n = 21), increasing the number of KRAS-positive patients from 24 to 92. This included 3 with negative tissue biopsies, 60 not assessed, and 5 who did not have enough tissue material.

The investigators noted liquid biopsy testing rescued 30.2% (n = 85) of patients, including those who did not have enough tissue material and those who were incompletely genotyped or negative for the biomarker in tissue.

“The downside of obtaining mutations from tissue biopsies is that usually if this testing is not done with a very powerful and comprehensive assay, such as next-generation sequencing, it is done in successive steps: one test after another, which frequently leads to depletion of the tissue sample,” Papadimitrakopoulou explained. “Therefore, you end up with testing that is not complete because the tissue is not enough for testing of all the biomarkers.”

In addition, the study found a positive-predictive value of 100% forEGFR, ALK, ROS1, andBRAFmutations, for which there are agents already approved to treat this patient population.

Time from test order to final results was a median 9 days with Guardant360 compared with 15 days with tissue-based testing.

The researchers acknowledged the study was limited by its comparison of liquid biopsy testing to a current standard-of-care tissue genotyping test and not the tissue-based next-generation sequencing test, adding “the study results are only applicable to the Guardant360 test and not other liquid biopsy tests,” according to an AACR press release.

The prospective, multicenter study evaluated whether Guardant360 can be used to detect all 7 guideline-recommended predictive biomarker mutations (EGFR,ALK,ROS1,BRAF,RET,MET, andERBB2) and 1 prognostic biomarker mutation (KRAS) at the same rate as traditional tissue genotyping tests in 282 patients with newly diagnosed advanced NSCLC enrolled at 28 North American centers between July 2016 to April 2018. Of the 282 patients who submitted a pre-treatment blood sample for cfDNA analysis, the majority were white (81.9%) and half were female (54.3%). Papadimitrakopoulou noted that clinical follow-up of the study is ongoing.

She concluded the study validates the clinical utility of cfDNA in newly diagnosed metastatic NSCLC. “What prompted the study was the desire to demonstrate that the liquid biopsy, which is easier to obtain and with a faster turnaround time, can detect these mutations and alterations in the DNA at a rate similar to the standard, which is tissue biopsy. That is something that is assumed to be true but was not tested in a clinical trial prospectively,” she added. “We felt there was a need for this since the desire to expand the group of patients who get these tests upfront is great. Having a test that we can rely upon to get good results for treatment choices is a very important step.”

AACR Annual Meeting 2019 director John D. Carpten, PhD, Institute of Translational Genomics, Keck School of Medicine, University of Southern California, noted how exciting these results are. “Non-invasive 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 biopsy or surgical resection. In this case, we can identify the mutations in the cancer that are important and do this in a much more noninvasive way.”

“It also reveals that that this field is rapidly growing with new methods that might also include epigenetic changes in cell-free DNA, circulating tumor cells, exosomes, and other forms of mRNA that may be circulating in plasma,” he added. “So, the integration of all these various measurements, we believe really allow us to do a much better job at identifying cancers, monitoring them, and identifying appropriate mutations or alterations that are tied to specific targeted therapies.”


Leighl N, Page RD, Raymond VM, et al. Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC). Presented at: AACR Annual Meeting 2019 media preview; Feb. 27, 2019; Philadelphia.