Clinical Outcomes for Plasma-Based Genomic Profiling versus Tissue Testing in Advanced NSCLC (NILE)

Therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published tissue-based targeted therapy clinical outcomes in non–small-cell lung cancer (NSCLC).

Expert guidelines recommend somatic genomic testing to inform targeted therapy treatment for patients with advanced lung adenocarcinoma. The NILE study was a prospective observational study that demonstrated noninferiority of cell-free circulating tumor DNA-based tumor genotyping compared with tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed advanced lung adenocarcinoma. At the American Society of Clinical Oncology 2021 annual meeting, researchers reported clinical outcomes data now that the NILE patient cohort has matured.1

NILE, a prospective multicenter North American study, enrolled patients with previously untreated advanced lung adenocarcinoma who underwent standard-of-care tissue genotyping and concurrent comprehensive cell-free circulating tumor DNA analysis using the commercially available Guardant360 assay (Guardant Health). After 12 months of study enrollment, data regarding objective response rate (ORR), disease control rate (DCR), and time to treatment were collected for patients with targetable genomic alterations as defined by National Comprehensive Cancer Network guidelines who were treated with community-based physician’s choice of therapy.1

Among 282 patients in the study, 32% had an actionable biomarker detected by tissue (21%) and/or cell-free circulating tumor DNA (27%) analysis.1 Sixty-one (69%) of these patients were treated with a US Food and Drug Administration–approved targeted therapy based on somatic genotyping results (ie,EGFR, ALK, ROS1 inhibitor).1 Thirty-three patients were eligible for clinical response evaluation and demonstrated an ORR of 58% and a DCR of 94%.1

Twenty-five patients in the evaluable cohort (76%) achieved a durable response of ≥6 months.1 Seventeen (52%) patients achieved a durable response of >12 months.1 Patients responded to targeted therapy regardless of the variant allele frequency of the target alteration.1 Time to treatment was significantly faster for cell-free circulating tumor DNA-informed biomarker detection compared with tissue genotyping (median, 18 vs 31 days, respectively; P = .0008).1

This is the first prospective community-based study to find that cell-free circulating tumor DNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and that therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published tissue-based targeted therapy clinical outcomes. The NILE study complements and confirms findings in the prospective FLAURA and SLLIP studies, which exclusively enrolled patients from academic sites.1


1. Page RD, Drusbosky L, Dada HI, et al. Clinical outcomes for plasma-based comprehensive genomic profiling versus tissue testing in advanced lung adenocarcinoma. Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9027.