利用ctDNA证据建立癌症药物研发的常设平台以监测复发
A standing platform for cancer drug development using ctDNA-based evidence of recurrence
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影响因子:66.8
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Nov
作者:
Arielle J Medford, Ariel B Carmeli, Alexandra Ritchie, Nikhil Wagle, Levi Garraway, Eric S Lander, Aparna Parikh
DOI:
10.1038/s41568-024-00742-2
摘要
临床试验所需时间限制了新治疗方案的评估和提供速度。开发新方法以提高试验效率，而不影响其科学严谨性，将惠及患者，尤其在肿瘤学中，辅助性试验有望拦截转移性疾病，但通常需要大量患者和多年时间。我们设想建立一个常设平台——一种支持持续识别和招募早期分子证据（MED）患者的基础设施，依据循环肿瘤DNA（ctDNA）检测早期疾病复发的证据。MED强烈预测随后的复发，大部分患者在18个月内出现影像学证据。这一平台将支持多种治疗的高效测试，从小型探索性研究到大型关键性试验。招募具有MED但尚无影像学证据的患者的试验，因复发概率高和时间短，可推动药物评价，且规模较小、速度较快。ctDNA还可能作为早期治疗效果的有价值生物标志物，从而实现小规模信号检测试验。本文探讨如何建立这样的平台。
Abstract
The time required to conduct clinical trials limits the rate at which we can evaluate and deliver new treatment options to patients with cancer. New approaches to increase trial efficiency while maintaining rigor would benefit patients, especially in oncology, in which adjuvant trials hold promise for intercepting metastatic disease, but typically require large numbers of patients and many years to complete. We envision a standing platform - an infrastructure to support ongoing identification and trial enrolment of patients with cancer with early molecular evidence of disease (MED) after curative-intent therapy for early-stage cancer, based on the presence of circulating tumour DNA. MED strongly predicts subsequent recurrence, with the vast majority of patients showing radiographic evidence of disease within 18 months. Such a platform would allow efficient testing of many treatments, from small exploratory studies to larger pivotal trials. Trials enrolling patients with MED but without radiographic evidence of disease have the potential to advance drug evaluation because they can be smaller (given high probability of recurrence) and faster (given short time to recurrence) than conventional adjuvant trials. Circulating tumour DNA may also provide a valuable early biomarker of treatment effect, which would allow small signal-finding trials. In this Perspective, we discuss how such a platform could be established.