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Liquid Biopsy Matches Tissue for NSCLC Guidance

— Increased mutation detection rate, faster turnaround time

MedpageToday

ATLANTA -- A liquid biopsy performed at least as well as tissue biopsies for guiding treatment decisions about newly diagnosed advanced lung cancer, a prospective comparison study showed.

Analysis of tissue biopsies identified guideline-recommended therapies for 21.3% of patients, whereas blood-based analysis of cell-free DNA (cfDNA) identified available therapies in 27.3% of cases. Use of liquid biopsies also reduced the waiting time for results by almost a week as compared with tissue assessments, reported Vassiliki Papadimitrakopoulou, MD, of the MD Anderson Cancer Center in Houston.

Given that the blood test is commercially available, the findings have potentially immediate implications for clinical practice, she stated.

"These results show that cell-free DNA can be used to completely and accurately assess and identify guideline-recommended biomarkers significantly faster than tissue testing, including identifying guideline-recommended biomarkers in patients with nondiagnostic tissue results," Papadimitrakopoulou said during a press briefing in advance of the (AACR) annual meeting, to be held here March 29-April 3.

"In the largest study of newly diagnosed advanced non-small cell lung cancer [NSCLC], these study results demonstrate the clinical utility of a well-validated, comprehensive, sensitive cell-free DNA test to identify patients with guideline-recommended biomarkers as an alliterative to standard-of-care tissue testing," she said.

No clinical or tumor characteristics would exclude the use of a liquid biopsy, she added. Whether the results are applicable to other types of cancer remains to be seen.

The study provided a demonstration of the power and potential clinical utility of new approaches for measuring circulating biomarkers for cancer detection and monitoring, and in this case, informing treatment decisions, said AACR press briefing co-moderator John D. Carpten, PhD, of the Keck School of Medicine at the University of Southern California in Los Angeles.

"This study revealed that noninvasive approaches are feasible," said Carpten, chair of the program committee for the 2019 meeting. "They meet standards that are minimally at the level of, if not superior, to more invasive approaches to disease detection. The need for genotyping of actual tissue specimens would require either a biopsy or surgical resection. [With a liquid biopsy] we can actually identify the mutations that are in the cancer that are really important and do this in a much more noninvasive way."

"The study also showed that this field is growing incredibly rapidly with new methods 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 measurements, we believe, will really allow us to do a much better job of identifying cancers, monitoring them, and identifying appropriate mutations or alterations that are tied to very specific targeted therapies."

Currently, about 30% of patients with newly diagnosed advanced NSCLC can be treated with targeted agents specific for certain tumor mutations or alterations. Selection of a targeted agent as first-line therapy for NSCLC requires assessment of an expanding list of guideline-recommended genomic biomarkers, said Papadimitrakopoulou. The current standard of care for identifying targetable mutations relies on availability of tumor tissue for analysis, which is limited by biopsy-related risks, lack of tissue, and time required for laboratory processing.

Investigators at 28 North American centers performed a prospective, multicenter clinical trial to compare conventional tissue assessment (determined by the treating physician) and a 73-gene next generation sequencing panel to assess cfDNA in blood (Guardant360). Patients with newly diagnosed advanced NSCLC had tumor assessment by both methods.

The study included 282 patients and had a primary endpoint of detection rate for guideline-recommended predictive biomarkers ("G7": EGFR, ALK, ROS1, BRAF, RET, MET, and ERBB2). Investigators also examined detection of non-G7 biomarkers, such as prognostic KRAS targets.

Tissue-based biopsies identified a guideline-supported biomarker in 60 patients, whereas the liquid biopsy identified targetable genomic alterations in 77 patients (P<0.0001). For the 60 patients with positive tissue biopsies, the biomarker was identified by the tissue specimen alone in 12 cases and by both the tissue and liquid biopsy in 48 cases. Use of the liquid biopsy increased the total number of patients with a recognized biomarker from 60 to 89, after accounting for patients who had negative tissue biopsies, who did not undergo a tissue biopsy, or who did not have sufficient tissue to analyze.

Among 193 patients whose tumors did not have G7 biomarkers, 24 (12.4%) had an activating KRAS alteration identified by tissue alone in three cases and by both biopsy techniques in 21 cases. The number of patients with KRAS alterations increased to 92 after accounting for negative tissue tests, patients who did not undergo tissue biopsy, or who had insufficient tumor tissue.

The median turn-around time for tissue biopsy results was 15 days. That decreased to nine days with liquid biopsy (P<0.0001).

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined ľֱ in 2007.

Disclosures

The study was funded by Guardant Health.

Papadimitrakopoulou disclosed relevant relationships with Nektar Therapeutics, AstraZeneca, Arrys Therapeutics, Merck, LOXO Oncology, Araxes Pharma, F. Hoffmann-La Roche, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Novartis, Takeda, AbbVie, TRM Oncology, Tesaro, Exelixis, Gritstone, Eli Lilly, Checkmate, and Incyte.

Primary Source

American Association for Cancer Research

Leighl N, 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)" AACR 2019.