Background

A recent phase II randomized Japanese study reported better survival with regorafenib followed at progression by cetuximab ± irinotecan compared with the reverse standard sequence in chemo-refractory and anti-EGFR-naïve, RAS wild-type (wt) mCRC patients. Nowadays the use of anti-EGFR antibodies is more frequently anticipated to the first-line of therapy especially in patients with left-sided RAS/BRAF wt tumours. However, retrospective analyses and phase II single-arm trials showed promising activity of re-using anti-EGFRs in metastatic colorectal cancer (mCRC) patients who previously achieved benefit from a first-line anti-EGFR-based treatment. Post-hoc analyses of these trials revealed that the detection of RAS mutations in circulating tumour DNA (ct-DNA) at the time of re-treatment may be useful to identify resistant patients.

Patients and Methods

PARERE (NCT04787341) is a prospective, open label, multicentre phase II study in which 214 RAS/BRAF wt chemo-refractory mCRC patients with previous benefit from first-line anti-EGFR-based treatment and RAS/BRAF wt ct-DNA in the liquid biopsy collected at the time of inclusion will be randomized in a 1:1 ratio to receive panitumumab followed after progression by regorafenib versus the reverse sequence. Primary endpoint is overall survival. Secondary endpoints are 1st-progression free-survival (PFS), 2nd-PFS, time to failure strategy, objective response rate, and safety.

Aim of the study

The aim of this study is to validate the role of anti-EGFR retreatment and its proper placement in the therapeutic route of mCRC patients selected according to the analysis of ct-DNA in liquid biopsy. Results are expected at the end of 2023.

中文翻译：

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PARERE 试验的基本原理和研究设计：在 RAS 和 BRAF 野生型化疗难治性转移性结直肠癌患者中帕尼单抗再治疗后继瑞戈非尼与逆序的随机 II 期研究

背景

最近的一项 II 期随机日本研究报告，与化疗难治性和抗 EGFR 初治的RAS野生型 (wt) mCRC 患者相比，瑞戈非尼在进展时接受西妥昔单抗 ± 伊立替康的生存期优于反向标准序列。如今，抗EGFR抗体的使用更频繁地被预期用于一线治疗，特别是在患有左侧RAS / BRAF wt肿瘤的患者中。然而，回顾性分析和 II 期单臂试验显示，在先前从一线抗 EGFR 治疗中获益的转移性结直肠癌 (mCRC) 患者中重复使用抗 EGFR 具有良好的活性。这些试验的事后分析表明，RAS的检测 再治疗时循环肿瘤 DNA (ct-DNA) 的突变可能有助于识别耐药患者。

患者和方法

PARERE (NCT04787341) 是一项前瞻性、开放标签、多中心 II 期研究，其中 214名RAS / BRAF wt 化学难治性 mCRC 患者先前受益于一线抗 EGFR 治疗和RAS / BRAF wt ct-DNA 在纳入时收集的液体活检将按 1:1 的比例随机接受帕尼单抗治疗，然后接受瑞戈非尼治疗，然后进行相反的治疗。主要终点是总生存期。次要终点是第一进展无生存期 (PFS)、第二次 PFS、故障时间策略、客观响应率和安全性。

研究目的

本研究的目的是验证抗 EGFR 再治疗的作用及其在根据液体活检中 ct-DNA 分析选择的 mCRC 患者治疗途径中的正确位置。结果预计在 2023 年底。