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Liquid biopsy comparable to tissue biopsy in detecting biomarkers in NSCLC
A liquid biopsy test accurately identified guideline-recommended biomarkers in metastatic non-small cell lung cancer at a rate similar to standard tissue tests, but with a shorter turnaround time, according to data from the NILE study scheduled for presentation at American Association for Cancer Research Annual Meeting.
“We know that about 30% of patients with newly diagnosed, advanced NSCLC have therapeutically targetable genomic alterations that make them eligible for targeted therapies,” Vassiliki Papadimitrakopoulou, MD, professor of thoracic/head and neck oncology at The University of Texas MD Anderson Cancer Center, said during a press cast. “Identifying these patients is important, as the response rate to properly identified targeted genomic therapy is higher than response rates to first-line chemotherapy or immune checkpoint therapy. Several professional guidelines obligate the assessment of these biomarkers for the proper selection of first-line treatment.”
Current standard-of-care testing depends on acquiring tissue samples, which can be invasive, result in inadequate specimens and require lengthy lab processing time.
In the prospective, multicenter, head-to-head study, Papadimitrakopoulou and colleagues sought to show the noninferiority of comprehensive cell-free DNA (cfDNA) analysis vs. standard tissue genotyping in identifying biomarkers among 282 patients (81.9% white; 54.3% women) with previously untreated, nonsquamous cell metastatic NSCLC.
Patients underwent standard genotyping and provided a pretreatment blood sample for cfDNA analysis using Guardant360 (Guardant Health), a 73-gene, next-generation sequencing panel.
The detection rate of guideline-recommended genomic biomarkers — including EGFR, ALK, ROS1, BRAF, RET, MET and ERBB2 — using standard-of-care tissue testing vs. Guardant360 served as the study’s primary endpoint.
Clinical follow-up occurred at 1 year or disease progression.
Standard tissue biopsy identified a guideline-recommended biomarker in 60 patients, whereas cfDNA detected a biomarker in 77 patients (21.3% vs. 27.3%; P < .0001).
cfDNA increased the total number of patients with a recognized guideline-recommended biomarker by 48%, from 60 patients to 89; this included patients whose tissue biopsies yielded results of negative (n = 7), not assessed (n =16) or insufficient quantity (n = 6).
Among the 193 patients who had no guideline-recommended biomarker by tissue biopsy or cfDNA, 24 (12.4%) showed an activating KRAS alteration detected in tissue alone (n = 3), or also in cfDNA (n = 21). With cfDNA, the number of KRAS-positive patients increased to 92 (tissue negative, n = 3; not assessed, n = 60; quantity not sufficient, n =5).
The cfDNA test demonstrated a positive predictive value of 100% for four biomarkers that are targets of FDA-approved therapies (EGFR, ALK, ROS1, BRAF).
Test turnaround time — defined as time from the test order to test results — was 9 days with cfDNA vs. 15 days with tissue genotyping (P < .0001).
Limitations of the study include the comparison of liquid biopsy testing with a current standard-of-care genotyping test rather than the tissue-based, next-generation sequencing test, and that these findings apply only to Guardant360 and not other liquid biopsy tests.
In an interview with HemOnc Today, Papadimitrakopoulou said these findings demonstrate that cfDNA can be used to accurately and completely evaluate and detect guideline-recommended biomarkers significantly faster than tissue biopsy.
“In the largest prospective, multicenter liquid biopsy study in previously untreated metastatic NSCLC, we have demonstrated that genotyping tumors via liquid biopsy detects actionable, guideline-recommended genomic alterations at a rate similar to tissue biopsy with significantly lower turnaround time,” she said.
“Advanced NSCLC is a uniformly deadly disease; therefore, getting patients on treatment as soon as possible is paramount,” Papadimitrakopoulou said in a press release. “Our results show that a highly sensitive and specific liquid biopsy should be part of the standard of care for these patients.” – by Jennifer Byrne
Reference:
Leighl N, et al. Abstract 4460. Scheduled for presentation at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta.
Disclosures: Guardant Health funded this study. Papadimitrakopoulou reports advisory board roles with AbbVie, Arrys Therapeutics, Araxes Pharma, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Exelis, F. Hoffman-LaRoche, Gritstone, Guardant Health, Janssen Research Foundation, Loxo Oncology, Nektar Therapeutics, Novartis, Takeda, Tesaro and TRM Oncology; a speaker/preceptors role with F. Hoffman LaRoche; and research support from AstraZeneca, Bristol-Myers Squibb, Checkmate, Eli Lilly, F. Hoffman-LaRoche, Guardant Health, Incyte, Janssen and Nektar Therapeutics. Please see the abstract for all other authors’ relevant financial disclosures.
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This is incredible work that shows the power of these new approaches in allowing us to measure circulating cell-free biomarkers for the detection, monitoring and, in this case, actual treatment choices for cancer.The results of this study are very exciting and reveal several important things. One is that noninvasive approaches are feasible, and they meet standards that are at the level of, if not superior to, more invasive approaches to disease detection. In this case, we can identify the cancer and identify the mutations of the cancer and do this is a less invasive way.
It also reveals that this field is growing incredibly rapidly, with new methods that might include measuring epigenetic changes in cell-free DNA, circulating tumor cells, and exosomes and other forms of mRNA that might be circulating in plasma. We can monitor these changes and identify appropriate mutations that are tied to very specific targeted therapies.It’s also great that they chose NSCLC for this study. It has been a scourge in the oncology community for so long, but now there are a number of targeted treatments available for these patients, in addition to immunotherapy.
Being able to use these new approaches for detecting and diagnosing cancer, and using this information to identify choices for treatment, is incredible.