Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy

作者：Jeffrey C. Thompson, Erica L. Carpenter, Benjamin A. Silva, J Rosenstein, Austin L. Chien, Katie Quinn, Carin R. Espenschied, Allysia J. Mak, Lesli A. Kiedrowski, Martina I. Lefterova, Rebecca J. Nagy, Sharyn I. Katz, Stephanie S. Yee, Taylor A. Black, Aditi P. Singh, Christine Ciunci, Joshua Bauml, Roger B. Cohen, Corey J. Langer, Charu Aggarwal · 发表于：JCO Precision Oncology · 年份：2021 · DOI：10.1200/po.20.00321 · 被引用次数：108 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics

PURPOSE Although the majority of patients with metastatic non–small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P < .001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P < .001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95%...