1. Fuerst, Mark L.

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ATLANTA-A liquid biopsy test detects all guideline-recommended biomarkers in newly diagnosed metastatic non-small cell lung cancer (NSCLC) at a rate similar to that of standard-of-care tissue genotyping tests and with a faster turnaround time. A single test identified one prognostic biomarker (KRAS mutations) and seven predictive biomarkers, including genomic alterations in ROS1, BRAF, RET, MET, ALK, EGFR, and ERBB2.

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"About 30 percent of lung cancers can now be treated with molecularly targeted therapies and the response rates using these treatments are much higher than with chemotherapy," said Vassiliki Papadimitrakopoulou, MD, Professor of Medicine in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. "But to identify patients who will benefit from these therapies, we need to ensure all patients are tested for these targetable mutations."


Papadimitrakopoulou presented the results of the study (Abstract 4460) at a media preview of the American Association of Cancer Research (AACR) Annual Meeting 2019.


"Selecting first-line therapy for patients with NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers. Standard-of-care testing relies on tissue, which is limited by biopsy-related risks, specimen insufficiency, and lab processing duration, which hamper timely optimal treatment selection," she noted.


A recent study showed that guideline-recommended testing was completed in only 8 percent of patients with NSCLC, which means that most patients and their clinicians do not have all of the information available to make an informed therapy decision, Papadimitrakopoulou explained.


"Tissue biopsy-based tests are invasive, can have serious complications, [and] are time-consuming, and the specimens are often inadequate to test for all the relevant mutations," she stated.


The researchers set out to demonstrate the non-inferiority of Guardant360, a well-validated, comprehensive, and highly sensitive liquid biopsy test that utilizes cell-free tumor DNA (cfDNA) in blood, relative to standard-of-care tissue genotyping to identify guideline-recommended genomic biomarkers in patients with metastatic NSCLC.


Research Details

The prospective, multi-center study, called Noninvasive versus Invasive Lung Evaluation (NILE), enrolled 282 patients with newly diagnosed, advanced NSCLC from 28 North American sites. At least one of the guideline-recommended biomarkers was detected in 60 patients using tissue-based tests alone. By adding Guardant360, the rate of detection increased by 48 percent, from 60 patients to 89 patients, which included those whose samples were negative by tissue (7), not tested (16), or did not have enough material (6) for the tissue-based tests.


The researchers also found that the cfDNA test results of four biomarkers (EGFR, ALK, ROS1, BRAF), for which there are FDA-approved drugs, were concordant with the tissue-based test results with a positive-predictive value of 100 percent. "These findings should give confidence to oncologists to trust Guardant360 as a testing option for treatment selection in NSCLC patients," said Papadimitrakopoulou.


Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 (12.4%) patients 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.


The test turnaround time, defined as time from test order to final results, was a median of 9 days for Guardant360 versus a median of 15 days for tissue-based testing.


"Our study shows that Guardant360 test results can be obtained in about a week, are reliable, and in some respects a better alternative to the traditional tissue testing in ensuring guideline-complete molecular testing for all patients," she stated. "This differential is meaningful to patients and clinicians, and in my recent clinical experience, I can do an initial consult with a patient on a Monday and have them back in the office the following Monday to start treatment.


"Advanced NSCLC is a uniformly deadly disease, therefore, getting patients on treatment as soon as possible is paramount. Our results show that a highly sensitive and specific liquid biopsy should be part of the standard of care for these patients," she added.


Study limitations include 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 other liquid biopsy tests.


In conclusion, Papadimitrakopoulou summarized: "In the largest study of newly diagnosed advanced NSCLC, these study results demonstrate the clinical utility of a cfDNA test to identify patients with guideline-recommended biomarkers as an alternative to standard-of-care tissue testing. 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 non-diagnostic tissue results, and demonstrates the clinical utility of cfDNA in newly diagnosed metastatic NSCLC."


Program Chair of the AACR Annual Meeting, John D. Carpten, PhD, Director, Institute of Translational Genomics, Keck School of Medicine, University of Southern California, commented: "The results of this study are exciting and reveal several important things. They show the power of new approaches to measure cfDNA for detection, monitoring, and treatment choices for cancer. 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. This also reveals that this field is growing incredibly rapidly with a new method that might also include measuring epigenetic changes in cfDNA, circulating tumor cells and exosomes, and other forms of mRNA that might be circulating in plasma.


"A number of therapies are available in NSCLC. To be able to use new approaches and information to identify treatment choices is incredible," he concluded.


Mark L. Fuerst is a contributing writer.