National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
BMC Cancer. 2019 Jun 28;19(1):640. doi: 10.1186/s12885-019-5826-7.
In the management of patients with RAS wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) therapies have demonstrated a clinical benefit, with longer survival. However, the correlation between the emergence of circulating RAS mutations and secondary resistance to anti-EGFR therapies requires further elucidation. In this study, we aim to examine evolutionary changes in RAS mutations through liquid biopsy in patients with mCRC during and after anti-EGFR therapy.
A total of 120 patients diagnosed with RAS wild-type mCRC will be enrolled in this study. Patients will receive a cetuximab-based infusional 5-fluorouracil regimen as first-line treatment. Cetuximab-based treatment is expected to continue until disease progression, intolerable toxic effects, or withdrawal of consent. Blood samples from enrolled patients will be collected before and then every 3 months during cetuximab-based treatment and also at disease progression. These blood samples will be evaluated for RAS resistance mutations by using the MassARRAY platform. The primary endpoint is the percentage of RAS mutations detected in circulating DNA from patients during cetuximab treatment. The correlation between the tumor response and survival outcomes of these patients and the emergence of circulating RAS mutations will be further analyzed.
Liquid biopsy is a powerful technology that can represent tumor heterogeneity in a relatively noninvasive manner. Because RAS mutations play a major role in resistance to anti-EGFR therapy for mCRC, examining evolutionary changes in these mutations during such treatment through liquid biopsy would be useful. After comprehensively analyzing the emergence of circulating RAS mutations and its clinical relevance in this study, our results should provide practical guidance on anti-EGFR therapy for mCRC.
The date of trial registration ( NCT03401957 ) in this study was January 17, 2018.
在 RAS 野生型转移性结直肠癌（mCRC）患者的治疗中，抗表皮生长因子受体（EGFR）治疗显示出临床获益，延长了生存期。然而，循环 RAS 突变的出现与抗 EGFR 治疗的继发耐药之间的相关性仍需进一步阐明。本研究旨在通过液体活检检测 mCRC 患者在接受抗 EGFR 治疗期间和之后循环 RAS 突变的演变。
本研究共纳入 120 例 RAS 野生型 mCRC 患者。患者将接受西妥昔单抗为基础的输注氟尿嘧啶方案作为一线治疗。预计西妥昔单抗治疗将持续到疾病进展、无法耐受的毒性作用或患者撤回同意。入组患者将在接受西妥昔单抗治疗前以及治疗期间每 3 个月采集血样，并且在疾病进展时采集血样。这些血样将通过 MassARRAY 平台评估 RAS 耐药突变。主要终点是在西妥昔单抗治疗期间从患者循环 DNA 中检测到的 RAS 突变的百分比。还将进一步分析这些患者的肿瘤反应和生存结果与循环 RAS 突变的出现之间的相关性。
液体活检是一种强大的技术，可以相对无创地代表肿瘤异质性。由于 RAS 突变在 mCRC 患者抗 EGFR 治疗耐药中起主要作用，因此通过液体活检检查这些突变在治疗过程中的演变将很有用。本研究全面分析循环 RAS 突变的出现及其临床相关性后，我们的结果应为 mCRC 患者的抗 EGFR 治疗提供实用指导。
本研究的试验注册日期（NCT03401957）为 2018 年 1 月 17 日。
