Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem, Belgium.
Integrated Personalized and Precision Oncology Network (IPPON), Center for Oncological Research (CORE), University of Antwerp and Antwerp University Hospital, Wilrijk, Belgium.
Clin Cancer Res. 2023 May 1;29(9):1741-1750. doi: 10.1158/1078-0432.CCR-22-1500.
Analysis of methylation markers in liquid biopsies is a promising technique for the follow-up of patients with metastatic colorectal cancer (mCRC), because they can be used in all patients, regardless of their mutational status. Therefore, we studied the value of NPY methylation analysis in circulating tumor DNA (ctDNA) for accurate response monitoring in patients with mCRC in the PANIB trial.
The PANIB trial was a randomized phase II trial designed to compare FOLFOX plus panitumumab and FOLFOX plus bevacizumab in patients with RAS wild-type unresectable mCRC. The results of sequential liquid biopsies were correlated with results of imaging.
Forty patients were included from six Belgian hospitals. Analysis of the liquid biopsies revealed that higher baseline levels of methylated ctDNA was associated with a significantly shorter overall survival [HR, 1.015; 95% confidence interval (CI), 1.005-1.025; P = 0.002]. Furthermore, 37 patients provided at least two liquid biopsies. Thirty-one of them showed a decrease in the methylation ratio after the start of therapy, which corresponded with stable disease or response on imaging at the first evaluation. When comparing the panitumumab and bevacizumab arm, significantly higher objective response and early tumor shrinkage rates were observed in the panitumumab arm (P = 0.048 and 0.015, respectively). However, due to a small study population, the trial was underpowered to detect a significant difference in survival.
The results of this study confirm that baseline methylated ctDNA is a prognostic marker and indicate that NPY methylation is a promising marker for response monitoring in patients with mCRC.
分析液体活检中的甲基化标记物是一种很有前途的技术，可用于监测转移性结直肠癌（mCRC）患者，因为无论突变状态如何，这些标记物都可以用于所有患者。因此，我们在 PANIB 试验中研究了 NPY 甲基化分析在循环肿瘤 DNA（ctDNA）中的价值，以准确监测 mCRC 患者的反应。
PANIB 试验是一项随机的 II 期试验，旨在比较 FOLFOX 加 panitumumab 与 FOLFOX 加 bevacizumab 用于 RAS 野生型不可切除 mCRC 患者。连续液体活检的结果与影像学结果相关。
从六个比利时医院纳入了 40 名患者。液体活检分析显示，较高的基线甲基化 ctDNA 水平与总生存期显著缩短相关[风险比，1.015；95%置信区间（CI），1.005-1.025；P=0.002]。此外，37 名患者至少提供了两份液体活检。其中 31 份在治疗开始后显示甲基化比值降低，这与影像学上的首次评估中疾病稳定或有反应相对应。当比较 panitumumab 和 bevacizumab 臂时，panitumumab 臂的客观缓解率和早期肿瘤退缩率显著更高（P=0.048 和 0.015）。然而，由于研究人群较小，该试验未能检测到生存率的显著差异。
这项研究的结果证实了基线甲基化 ctDNA 是一个预后标志物，并表明 NPY 甲基化是监测 mCRC 患者反应的一个很有前途的标志物。
