论文标题
Droid：优化肿瘤学药物开发剂量的剂量范围方法
DROID: Dose-ranging Approach to Optimizing Dose in Oncology Drug Development
论文作者
论文摘要
在有针对性疗法的时代，人们对基于“ More Is Better”范式的肿瘤学药物的开发一直在越来越关注，该范式是几十年前用于化学疗法的。最近，美国食品药品监督管理局（FDA）启动了Optimus项目，以改革肿瘤学药物开发中的剂量优化和剂量选择范式。为了适应这种范式转移，我们提出了一种剂量范围的方法来优化剂量（DROID），用于使用靶向药物进行肿瘤学试验。 Droid利用良好的剂量范围的研究框架，该框架通常用于开发非肿瘤学药物数十年，并与已建立的肿瘤学剂量调查设计桥梁，以优化肿瘤学药物的剂量。 Droid由两个无缝连接的阶段组成。在第一阶段，患者被依次招募并自适应地分配给研究剂量，以建立治疗剂量范围（TDR），定义为具有可接受的毒性和效力谱的剂量范围，以及建议的2期剂量集（RP2S）。在第二阶段，患者被随机分配给RP2中的剂量，以评估剂量反应关系并确定最佳剂量。仿真研究表明，机器人大大胜过常规方法，提供了一种新的范式，以有效地优化靶向肿瘤药物的剂量。
In the era of targeted therapy, there has been increasing concern about the development of oncology drugs based on the "more is better" paradigm, developed decades ago for chemotherapy. Recently, the US Food and Drug Administration (FDA) initiated Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development. To accommodate this paradigm shifting, we propose a dose-ranging approach to optimizing dose (DROID) for oncology trials with targeted drugs. DROID leverages the well-established dose-ranging study framework, which has been routinely used to develop non-oncology drugs for decades, and bridges it with established oncology dose-finding designs to optimize the dose of oncology drugs. DROID consists of two seamlessly connected stages. In the first stage, patients are sequentially enrolled and adaptively assigned to investigational doses to establish the therapeutic dose range (TDR), defined as the range of doses with acceptable toxicity and efficacy profiles, and the recommended phase 2 dose set (RP2S). In the second stage, patients are randomized to the doses in RP2S to assess the dose-response relationship and identify the optimal dose. The simulation study shows that DROID substantially outperforms the conventional approach, providing a new paradigm to efficiently optimize the dose of targeted oncology drugs.
