“药物重发现”计划可促进现有抗癌药物的拓展使用，这一成果由荷兰癌症研究所E. E. Voest研究组近期取得。该成果于2019年9月30日在线发表于国际学术期刊《自然》。
研究人员介绍，肿瘤的大规模基因谱分析可以鉴定出可能有效的突变，并且这些突变已获得了批准的抗癌药物。但是，当带有这些突变的患者使用其批准范围之外药物治疗时，靶向治疗的成功和失败将不会被系统地收集或共享。
因此，研究人员启动了“药物重发现”计划，这是一项适应性、精确肿瘤学试验，旨在确定具有明确肿瘤类型和分子突变的患者队列中的活动信号，这些患者正在接受其批准范围以外的抗癌药物治疗。为了符合该试验的资格，患者必须已经用尽或拒绝了标准疗法，并且患有具有潜在可操作突变的恶性肿瘤，但尚无针对性的抗癌药物。
研究人员发现215名接受治疗的患者（包括136例接受靶向疗法的患者和79例接受免疫疗法的患者）的总临床获益率（定义为完全或部分响应，或病情稳定超过16周）占34％。临床获益的总体中位持续时间为9个月（95％置信区间为8-11个月），包括26名在数据截止时仍在持续获得临床获益的患者。通过鉴定一组成功接受了nivolumab（临床获益率为63％）的微卫星不稳定肿瘤患者和一组突变负荷相对较低的结直肠癌患者并且免疫疗法收效有限的成功案例，研究人员证明了药物重发现计划的潜力。药物重发现计划可促进在罕见癌症亚群中超出其范围的已批准药物的明确使用，鉴定这些亚群中的早期活动信号，加速新见解的临床转化，即在其已批准范围外使用抗癌药物，并创造可公开获取的知识库用于将来的决策。
附：英文原文
Title: The Drug Rediscovery protocol facilitates the expanded use of existing anticancer drugs
Author: D. L. van der Velden, L. R. Hoes, H. van der Wijngaart, J. M. van Berge Henegouwen, E. van Werkhoven, P. Roepman, R. L. Schilsky, W. W. J. de Leng, A. D. R. Huitema, B. Nuijen, P. M. Nederlof, C. M. L. van Herpen, D. J. A. de Groot, L. A. Devriese, A. Hoeben, M. J. A. de Jonge, M. Chalabi, E. F. Smit, A. J. de Langen, N. Mehra, M. Labots, E. Kapiteijn, S. Sleijfer, E. Cuppen, H. M. W. Verheul, H. Gelderblom, E. E. Voest
Issue&Volume: 2019-09-30
Abstract: The large-scale genetic profiling of tumours can identify potentially actionable molecular variants for which approved anticancer drugs are available13. However, when patients with such variants are treated with drugs outside of their approved label, successes and failures of targeted therapy are not systematically collected or shared. We therefore initiated the Drug Rediscovery protocol, an adaptive, precision-oncology trial that aims to identify signals of activity in cohorts of patients, with defined tumour types and molecular variants, who are being treated with anticancer drugs outside of their approved label. To be eligible for the trial, patients have to have exhausted or declined standard therapies, and have malignancies with potentially actionable variants for which no approved anticancer drugs are available. Here we show an overall rate of clinical benefitdefined as complete or partial response, or as stable disease beyond 16 weeksof 34% in 215 treated patients, comprising 136 patients who received targeted therapies and 79 patients who received immunotherapy. The overall median duration of clinical benefit was 9 months (95% confidence interval of 811 months), including 26 patients who were experiencing ongoing clinical benefit at data cut-off. The potential of the Drug Rediscovery protocol is illustrated by the identification of a successful cohort of patients with microsatellite instable tumours who received nivolumab (clinical benefit rate of 63%), and a cohort of patients with colorectal cancer with relatively low mutational load who experienced only limited clinical benefit from immunotherapy. The Drug Rediscovery protocol facilitates the defined use of approved drugs beyond their labels in rare subgroups of cancer, identifies early signals of activity in these subgroups, accelerates the clinical translation of new insights into the use of anticancer drugs outside of their approved label, and creates a publicly available repository of knowledge for future decision-making.
DOI: 10.1038/s41586-019-1600-x
Source: https://www.nature.com/articles/s41586-019-1600-x
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
