RNA Expression-based Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal Cancer Treated with Regorafenib and Nivolumab.
RNA Expression-based Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal Cancer Treated with Regorafenib and Nivolumab.
复制标题
基于 RNA 表达的分析可预测接受瑞戈非尼和纳武单抗治疗的转移性错配修复有效的结直肠癌患者的反应。
作者：
Miao,Ruoyu;Kim,DaeWon;Yu,James;Malafa,Mokenge;Mehta,Rutika;Strosberg,Jonathan;Imanirad,Iman;Iyer,Seema;Uhlik,Mark;Benjamin,Laura;Kim,Richard
我们之前进行了一项I/Ib期研究（NCT 03712943），在难治性转移性错配修复（pMMR）结直肠癌（CRC）患者中使用瑞戈非尼和纳武单抗。本研究旨在研究Xerna™ TME Panel在预测治疗反应中的作用。方法将22份存档预处理肿瘤样本进行Xerna™ TME Panel，这是一种基于机器学习的RNA测序生物标志物测定。评估Xerna肿瘤微环境（TME）亚型与总生存期（OS）、无进展生存期（PFS）、疾病控制率（DCR）和其他生物标志物（包括TME中的KRAS、PD-L1、CD 8表达和Treg细胞）的相关性。血管生成（A）亚型5例，免疫沙漠亚型7例，生物标志物阴性。虽然未达到统计学显著性，但Xerna TME生物标志物阳性患者的中位PFS（7.9 vs. 4.1个月，p= 0.254）、中位OS（15.75 vs. 11.9个月，p= 0.378）和DCR较高（70% vs. 58%，p= 0.675）。在我们的队列中IA亚型具有较高水平的CD 4 + FOXP 3 + Treg细胞，而A亚型显示较低水平的Treg cells.ConclusionXerna™ TME Panel分析在用瑞格非尼加纳武单抗治疗的难治性转移性pMMR CRC患者中可能具有预测临床益处的价值。需要进一步的研究来评估Xerna™ TME Panel分析在难治性转移性pMMR CRC患者中的预测作用。
IntroductionWe previously conducted a phase I/Ib study (NCT03712943) with regorafenib and nivolumab in patients with refractory metastatic mismatch repair proficient (pMMR) colorectal cancer (CRC). This study aimed to investigate the role of Xerna™ TME Panel in predicting the treatment response.MethodsTwenty-two archival pretreatment tumor samples were subjected to the Xerna™ TME Panel, a machine learning-based RNA-sequencing biomarker assay. The Xerna tumor microenvironment (TME) subtypes were evaluated for correlation with overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and other biomarkers including KRAS, PD-L1, CD8 expression, and Treg cells in TME.ResultsBased on Xerna™ TME Panel, 4 patients with immune-active (IA) subtype and 6 patients with immune-suppressed subtype were classified as biomarker-positive, and five with angiogenic (A) subtype and seven with immune desert subtype were biomarker-negative. While not reaching statistical significance, Xerna TME biomarker-positive patients seemed to have longer median PFS (7.9 vs. 4.1 months, p= 0.254), median OS (15.75 vs. 11.9 months, p= 0.378), and higher DCR (70% vs. 58%, p= 0.675). The IA subtype in our cohort had higher levels of CD4+ FOXP3+ Treg cells, whereas the A subtype showed lower levels of Treg cells.ConclusionXerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC who were treated with regorafenib plus nivolumab might be of value for predictive clinical benefit. Further studies are needed to evaluate the predictive role of Xerna™ TME Panel analysis in patients with refractory metastatic pMMR CRC.