使用基于CTDNA的复发证据进行癌症药物开发的常规平台
A standing platform for cancer drug development using ctDNA-based evidence of recurrence
影响因子:66.80000
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
摘要
进行临床试验所需的时间限制了我们可以评估并向癌症患者提供新的治疗选择的速度。提高试验效率同时保持严格性的新方法将使患者受益，尤其是在肿瘤学上，辅助试验有望拦截转移性疾病，但通常需要大量患者，并且需要多年才能完成。我们设想了一个站立平台 - 一种基础设施，以基于循环肿瘤DNA的存在，在治愈疗法治疗后治疗早期癌症治疗后，具有早期分子疾病（MED）的癌症患者的持续鉴定和试验。 MED强烈预测随后的复发，绝大多数患者在18个月内显示出疾病的射线照相证据。这样的平台将允许对许多治疗方法进行有效的测试，从小型探索性研究到更大的关键试验。招募药物患者但没有射线照相证据的试验可能会提高药物评估，因为它们可能比常规辅助试验更小（鉴于很高的复发概率）和更快的（短时间复发时间）。循环肿瘤DNA还可以提供有价值的治疗效果的早期生物标志物，这将允许进行小型信号调查试验。从这个角度来看，我们讨论了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.