Circulating tumor DNA evaluated by Next-Generation Sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer

OncoImmunology

Violaine Giraud¹  Jennifer Dumoulin¹  Etienne Giroux Leprieur¹  Sylvie Labrune¹  Thierry Chinet¹  Coraline Dumenil¹  Catherine Julie²  Julie Tisserand²  Jean-François Emile²  Guillaume Herbretau³  Hélène Blons³ 

[1] APHP – Ambroise Pare Hospital;EA4340, Biomarqueursen Cancérologie et Onco-Hématologie, UVSQ, Paris-Saclay University;INSERM UMR-S1147, CNRS SNC 5014, Saints-Pères Research Center, 45 rue des Saints-Pères Paris-Descartes University, Sorbonne Paris Cité University;

关键词: nivolumab;    circulating tumor dna;    anti-pd1;    immune checkpoint inhibitor;    tumor response;    clinical benefit;    somatic mutation;    non-small cell lung cancer;    next-generation sequencing;   

DOI  :  10.1080/2162402X.2018.1424675

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown