Clinical validation and utility of InVision ctDNA in advanced non-small cell lung cancer (NSCLC) patients
Authors: J. Remon, L. Mezquita, D. Planchard, C. Jovelet, L. Lacroix, E. Rouleau, K. Howarth, V. Plagnol, C. Morris, E. Green, C. Le Pechoux, C. Caramella, J. Adam, B. Besse
Journal: Annals of Oncology (2018)

Background: Molecular profiling using liquid biopsy ctDNA is rapidly gaining traction in routine clinical practice. However, there has been variable degree of accuracy and performance published to date and lack of prospective data on clinical outcomes for patients with actionable genomic alterations in ctDNA biopsies. Here, we describe the clinical validation and utility of InVision platform (InvisionFirst™-Lung, InvisionSeq™-Lung) in a large prospective cohort of advanced NSCLC patients. Methods: We performed a prospective, single-centre, observational study enrolling advanced NSCLC patients including treatment-naïve, on TKI treatment or at progression. ctDNA molecular analysis was performed using amplicon-based NGS (InVision platform) and where available, in tissue by Sanger sequencing or sensitive validated allele-specific technique. Clinical validation was performed for core gene variants of EGFR Exons 18-21, BRAF V600, MET Exon 14, ERBB2 Ins 20, ALK & ROS1 fusions, KRAS and STK11. Patients treated with matched targeted therapies evaluable for disease control at 3 months were collated for outcome analyses. Results: Of 362 advanced NSCLC patients recruited, 172 were treatment-naïve, and 190 were pre-treated patients with known tissue molecular profile (EGFR, BRAF, ALK, ROS1). For clinically-relevant gene variants, concordance agreement between ctDNA and tumor tissue analysis was 95% with 75% sensitivity and 97% specificity. Of 58 evaluable patients analysed to date, 83% had disease control at 3 months of therapy, with response rate and median progression free survival of 61% and 5.7 months, respectively.Table: 30PKey gene variantsTissue and LiquidTissue onlyLiquid onlyNo callPPVNPVSensitivitySpecificityConcordanceEGFR Exons18-217127877.898.887.5 (0.473-0.997)97.5 (0.913-0.997)96.6 (0.904-0.993)BRAF V600E12075NA0.6733.3 (0.084-0.957) 84-0.900100 (0.952-100)97.4 (0.910-0.997)ERBB2 Exon 2020049100.0100.0100.0 (0.158-1)100.0 (0.927-1)100.0 (0.930-1)MET Exon1412045100.095.833.3 (0.008-0.906)100.0 (0.921-1)95.8 (0.875-0.995)ALK fusion85NANA61.5 (0.316-0.987)NANAROS1 fusion11NANA50.0 (0.126-0.987)NANAKRAS22375675.995.088.0 (0.688-0.975)88.9 (0.784-0.954)88.64 (0.801-0.944)STK112121766.794.766.7 (0.094-0.992)94.4 (0.727-0.999)90.5 (0.696-0.988)Core gene variants44141032081.595.875.9 (0.628-0.861)97.0 (0.945-0.985)93.8 (0.909-0.960)Overall panel642736107864.097.670.3 (0.598-0.795)96.8 (0.955-0.977)94.8 (0.934-0.960) Open table in a new tab Conclusions: Our data endorses ctDNA molecular profiling using InVision as an accurate and reliable tool for the detection of clinically relevant molecular alterations in advanced NSCLC patients, with clinical outcomes consistent with expectations based on historical tissue profiling. Legal entity responsible for the study: Gustave Roussy. Funding: Inivata Ltd. Disclosure: K. Howarth, V. Plagnol, C. Morris, E. Green: Inivata employee and shareholder. All other authors have declared no conflicts of interest.