Abstract
According to the prospective NILE study, cell-free DNA analyses are at least as good as tissue-based genotyping for identifying therapeutically actionable genomic alterations in patients with non–small cell lung cancer; the turnaround time is also significantly shorter.
Findings from the prospective multicenter NILE study suggest that when it comes to pinpointing therapeutically actionable genomic alterations in patients with non–small cell lung cancer (NSCLC), cell-free DNA (cfDNA) analyses are at least as good as standard tissue-based genotyping. The turnaround time is also considerably shorter.
“Traditional tissue genotyping can take upwards of 30 days and is also limited by the risks associated with an invasive procedure,” said Vassiliki Papadimitrakopoulou, MD, who presented the results during a media preview of the American Association for Cancer Research Annual Meeting 2019, held in Atlanta, GA, March 29–April 3. “By contrast, cfDNA testing involves just a regular blood draw from patients, and results are usually available within a week.”
A total of 282 patients with newly diagnosed advanced NSCLC were enrolled in NILE, said Papadimitrakopoulou, chief of thoracic medical oncology at The University of Texas MD Anderson Cancer Center in Houston. Study participants underwent standard tissue genotyping as well as cfDNA analyses, the latter with Guardant360 (Guardant Health), a comprehensive liquid biopsy test that can detect alterations in 73 genes, including all nine predictive biomarkers for NSCLC—EGFR, ALK, ROS1, BRAF, RET, HER2, and NTRK mutations, as well as MET amplification and exon 14 skipping—currently recommended by National Comprehensive Cancer Network guidelines.
These biomarkers encompass “about 30% of all patients with NSCLC,” Papadimitrakopoulou noted, “so identifying them is important, because we know their response rates to the appropriate targeted drugs are higher than that seen with chemotherapy or immune checkpoint blockade.” In this head-to-head study, tissue genotyping picked up predictive biomarkers in 21.3% of patients; with Guardant360, the detection rate was 27.3%. The median turnaround time for tissue testing was 15 days, compared with 9 days for liquid biopsy.
“We also wanted to investigate the validity of our cfDNA results,” Papadimitrakopoulou said. “Focusing on EGFR, ALK, ROS1, and BRAF, we saw that if one of these biomarkers was found via liquid biopsy, it was also identified in tissue every single time. In other words, plasma cfDNA testing had a 100% positive predictive value in our study.”
Overall, NILE's results “have veryexciting implications for clinical practice,” Papadimitrakopoulou concluded. “In terms of making timely and optimal treatment choices, we think Guardant360 offers an excellent alternative to standard testing—especially in light of the expanding number of biomarkers that need to be assessed in NSCLC, often sequentially, which strains tissue availability.”
John Carpten, PhD, who heads the Institute of Translational Genomics at the University of Southern California in Los Angeles, agreed. “We've now seen that noninvasive approaches are feasible,” he said, “not only to detect and monitor cancer, but also to tailor its clinical management.”
The field of circulating biomarkers is one that's growing rapidly, Carpten added, with “new methods with which we can characterize exosomes, for instance, or measure epigenetic changes in cfDNA. Integrating these different tools should allow us to do a much better job in precision oncology.” –Alissa Poh
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