精准肿瘤学的进步导致肿瘤不可知分子引导治疗方案（MGTO）获得批准。声称具有肿瘤不可知潜力的最低要求仍然难以捉摸。欧洲肿瘤内科学会 (ESMO) 精准医学工作组 (PMWG) 协调了一个优化肿瘤不可知药物开发的项目。国际专家检查并总结了截至 2023 年 12 月美国食品和药物管理局和/或欧洲药品管理局批准的肿瘤不可知适应症监管评估所用的公开数据。最低客观缓解率 (ORR) 的不同情况，评估了所研究的肿瘤类型的数量，以及每种肿瘤类型的可评估患者的数量，以开发与肿瘤无关的潜力的筛查工具。该工具使用 2024 年上半年批准的肿瘤不可知适应症进行了测试。MGTO 的分类和肿瘤不可知药物开发的框架已经概念化。每种肿瘤不可知适应症都有至少在以下一种情况下建立客观反应的数据：三分之二 (≥4) 的研究肿瘤类型中有 5 名患者 (ORR ≥ 20%)，每种肿瘤类型至少有 5 名可评估患者。经过测试的适应症满足了这些最低要求，并且可以作为肿瘤不可知潜力的筛选工具，需要进一步验证。我们提出了一种概念分类法，根据通过靶向肿瘤驱动分子畸变所获得的治疗效果及其通过肿瘤特异性生物学的调节来对 MGTO 进行分类：肿瘤不可知、肿瘤调节或肿瘤限制。生物学相关的机制原理、早期监管建议和充分的试验设计（证明生物学驱动的肿瘤不可知活性的迹象）以及随后的证实性证据，应该成为肿瘤不可知药物开发的原则。ESMO 肿瘤不可知分类器(ETAC) 专注于靶向驱动分子畸变和肿瘤特异性生物学调节 MGTO 治疗效果的相互作用。我们提出了筛选肿瘤不可知潜力 (ETAC-S) 的最低要求，作为肿瘤不可知药物开发的一部分。 ETAC 截止值的定义是有保证的。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Advances in precision oncology led to approval of tumour-agnostic molecularly guided treatment options (MGTOs). The minimum requirements for claiming tumour-agnostic potential remain elusive.The European Society for Medical Oncology (ESMO) Precision Medicine Working Group (PMWG) coordinated a project to optimise tumour-agnostic drug development. International experts examined and summarised the publicly available data used for regulatory assessment of the tumour-agnostic indications approved by the US Food and Drug Administration and/or the European Medicines Agency as of December 2023. Different scenarios of minimum objective response rate (ORR), number of tumour types investigated, and number of evaluable patients per tumour type were assessed for developing a screening tool for tumour-agnostic potential. This tool was tested using the tumour-agnostic indications approved during the first half of 2024. A taxonomy for MGTOs and a framework for tumour-agnostic drug development were conceptualised.Each tumour-agnostic indication had data establishing objective response in at least one out of five patients (ORR ≥ 20%) in two-thirds (≥4) of the investigated tumour types, with at least five evaluable patients in each tumour type. These minimum requirements were met by tested indications and may serve as a screening tool for tumour-agnostic potential, requiring further validation. We propose a conceptual taxonomy classifying MGTOs based on the therapeutic effect obtained by targeting a driver molecular aberration across tumours and its modulation by tumour-specific biology: tumour-agnostic, tumour-modulated, or tumour-restricted. The presence of biology-informed mechanistic rationale, early regulatory advice, and adequate trial design demonstrating signs of biology-driven tumour-agnostic activity, followed by confirmatory evidence, should be the principles for tumour-agnostic drug development.The ESMO Tumour-Agnostic Classifier (ETAC) focuses on the interplay of targeted driver molecular aberration and tumour-specific biology modulating the therapeutic effect of MGTOs. We propose minimum requirements to screen for tumour-agnostic potential (ETAC-S) as part of tumour-agnostic drug development. Definition of ETAC cut-offs is warranted.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.