ABSTRACT

Introduction

Advances within molecular diagnostics have enabled us to identify a number of oncogenic drivers across different cancers. Many cancers can now be divided into subgroups based on molecular characteristics, and an increasing number of targeted anticancer drugs have been developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. With the recent approval of entrectinib, larotrectinib, and pembrolizumab for site-agnostic indications, biomarker-guided drug development has entered into a new phase.

Areas covered

The review focuses on the general principles of drug-diagnostic codevelopment, especially basket trials and site-agnostic drug development. Special attention is paid to entrectinib, larotrectinib, and pembrolizumab.

Expert opinion

The recent approval of entrectinib, larotrectinib, and pembrolizumab must be regarded as a paradigm shift in biomarker-guided oncology drug development. For a site-agnostic indication, it is important to have in mind the central role of the companion diagnostic (CDx), as the assay defines the ‘disease’ and the patient population to be treated. A number of site-agnostic drugs are currently in development and here, it is important that CDx assay development is given high priority, so an analytical and clinical validated assay is available at the time of drug approval.

中文翻译：

---

位点不可知的生物标志物引导的肿瘤药物开发。

摘要

介绍

分子诊断领域的进步使我们能够识别不同癌症中的许多致癌驱动因素。许多癌症现在可以根据分子特征分为亚组，并且已经开发出越来越多的靶向抗癌药物以及使用药物诊断共同开发模型的预测性生物标志物测定。随着近期 entrectinib、larotrectinib 和 pembrolizumab 获批用于部位不可知适应症，生物标志物引导的药物开发进入了一个新阶段。

覆盖区域

该综述侧重于药物诊断联合开发的一般原则，尤其是篮子试验和部位不可知药物开发。特别关注 entrectinib、larotrectinib 和 pembrolizumab。

专家意见

最近 entrectinib、larotrectinib 和 pembrolizumab 的批准必须被视为生物标志物引导的肿瘤药物开发的范式转变。对于部位不可知的适应症，重要的是要记住伴随诊断 (CDx) 的核心作用，因为该检测定义了“疾病”和要治疗的患者群体。许多位点不可知药物目前正在开发中，在这里，重要的是要高度重视 CDx 检测的开发，因此在药物批准时可以使用经过分析和临床验证的检测。