Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non-Small Cell Lung Cancer.

Abstract Background : Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced non-squamous non-small cell lung cancer (aNSCLC). The NILE study was a prospective observational study that demonstrated non-inferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed non-squamous aNSCLC. As the cohort has matured, clinical outcomes data can now be analyzed. Methods : This prospective, multicenter North American study enrolled patients with previously untreated non-squamous aNSCLC who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis (Guardant360). Patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician's choice of therapy had objective response rates, disease control rate, and time to treatment collected and compared to published outcomes. Results : Among 282 patients, 89 (31.6%) had an actionable biomarker, as defined by NCCN, detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these were treated with an FDA-approved targeted therapy guided by somatic genotyping results (EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) and 17 (52%) achieved a durable response > 6 months and 12 months, respectively. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (18 vs 31 days, respectively; p=0.0008). Conclusions : cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published targeted therapy outcomes with tissue profiling, even in community-based centers. Micro Abstract : Challenges remain with collecting adequate tissue biopsies to successfully perform comprehensive genomic profiling to identify NCCN-recommended biomarkers to inform first-line therapy in patients with newly diagnosed, advanced NSCLC. Plasma-based genotyping (liquid biopsy) has previously demonstrated non-inferiority to tissue biopsy for identifying targetable biomarkers in patients with NSCLC and achieves genotyping at a faster rate than tissue. This study analyzed clinical outcomes of 33 patients who were treated with targeted therapy in the first-line setting based on liquid biopsy results and demonstrated that patients respond to therapy at rates similar to those treated based on tissue-genotyping results, while able to initiate targeted therapy significantly faster (18 vs 31 days, respectively). These findings support the utility of liquid biopsy at diagnosis of advanced disease to inform targeted therapy options in a fast, non-invasive manner.