Nivolumab is an anti-PD1 antibody, given in second-line or later treatment in advanced
non-small cell lung cancer (NSCLC). The objective of this study was to describe the predictive value of
circulating tumor DNA (ctDNA) on the efficacy of
nivolumab in advanced NSCLC. We prospectively included all consecutive patients with advanced NSCLC treated with
nivolumab in our Department between June 2015 and October 2016. Plasma samples were obtained before the first injection of
nivolumab and at the first
tumor evaluation with
nivolumab. ctDNA was analyzed by Next-Generation Sequencing (NGS), and the predominant somatic mutation was followed for each patient and correlated with
tumor response, clinical benefit (administration of
nivolumab for more than 6 months), and progression-free survival (PFS). Of 23 patients, 15 had evaluable NGS results at both times of analysis. ctDNA concentration at the first
tumor evaluation and ctDNA change correlated with
tumor response, clinical benefit and PFS. ROC curve analyses showed good diagnostic performances for
tumor response and clinical benefit, both for ctDNA concentration at the first
tumor evaluation (
tumor response: positive predictive value (PPV) at 100.0% and negative predictive value (NPV) at 71.0%; clinical benefit: PPV at 83.3% and NPV 77.8%) and the ctDNA change (
tumor response: PPV 100.0% and NPV 62.5%; clinical benefit: PPV 100.0% and NPV 80.0%). Patients without ctDNA concentration increase >9% at 2 months had a long-term benefit of
nivolumab. In conclusion, NGS analysis of ctDNA allows the early detection of
tumor response and long-term clinical benefit with
nivolumab in NSCLC.