荷兰癌症研究所E. E. Voest小组取得一项新突破。他们的研究开发出了基因组学指导的说明书外治疗的前瞻性评价。2026年4月15日出版的《自然》发表了这项成果。

在这里，该研究组展示了2016年7月至2024年5月期间在DRUP试验中开始使用37种不同的超说明书药物治疗的1610名患者的结果。在这些患者中，1363例反应可评估，其中533例（39.1%）患有罕见癌症。临床获益率（确诊缓解或病情稳定至少16周）为34.9%(95%可信区间，32.2-37.6)，客观缓解率为15.7%（95%可信区间，13.7-17.9）。中位无进展生存期和总生存期分别为3.4个月（95%可信区间，2.8-3.5）和8.2个月（95%可信区间，7.6-8.8）。28.4%的患者发生了3级或更高级别的治疗相关不良事件。

值得注意的是，DRUP中产生的证据以荷兰监管机构的报销决定为主题。尽管在所有肿瘤-药物联合治疗中活性都不大，但定义的分子亚群和特殊应答者（7.0%）获得了有意义的益处。为了最大限度地提高患者的利益，研究人员建议超说明书精准药物应该只在系统评估疗效和毒性的框架内进行主题，支持生物标志物的改进，并能够逐步评估潜在的未来标签扩展。这些框架应优先考虑高可信度目标、早期干预、符合监管的终点和国际合作。

据介绍，抗癌药物通常是针对基因上与已批准适应症相似的肿瘤的标签外药物。然而，很少系统地捕捉结果，限制了基于证据的决策，并冒着重复无效治疗的风险。药物再发现方案（DRUP; ClinicalTrials.gov ID: NCT02925234）对荷兰晚期实体瘤患者进行了前瞻性评估，这些患者缺乏标准治疗方案，并且存在可操作的基因组改变。

附：英文原文

Title: Prospective evaluation of genomics-guided off-label treatment

Author: Verkerk, K., Spiekman, A. C., Haj Mohammad, S. F., Verbeek, F. A. J., Timmer, H., van Maren, M. A., Zeverijn, L. J., Geurts, B. S., van der Noort, V., Roepman, P., Jansen, A. M. L., de Leng, W. W. J., Gelderblom, H., Verheul, H. M. W., Voest, E. E.

Issue&Volume: 2026-04-15

Abstract: Anticancer drugs are frequently used off-label for tumours that are genetically similar to the approved indication. However, outcomes are rarely captured systematically, limiting evidence-based decision-making and risking repeated futile treatment. The Drug Rediscovery Protocol (DRUP; ClinicalTrials.gov ID: NCT02925234) prospectively evaluates such off-label use in patients in the Netherlands with advanced solid tumours who lack standard treatment options and harbour actionable genomic alterations1. Here we present results of 1,610 patients who began treatment with 37 different off-label drugs between July 2016 and May 2024 in the DRUP trial. Of these patients, 1,363 were response-evaluable, including 533 (39.1%) with rare cancers. The clinical benefit rate (confirmed response or stable disease for at least 16 weeks) was 34.9% (95% confidence interval, 32.2–37.6) and the objective response rate was 15.7% (95% confidence interval, 13.7–17.9). Median progression-free and overall survival were 3.4 months (95% confidence interval, 2.8–3.5) and 8.2 months (95% confidence interval, 7.6–8.8), respectively. Grade 3 or higher treatment-related adverse events occurred in 28.4% of patients. Notably, evidence generated in DRUP was used for reimbursement decisions by the regulatory bodies in the Netherlands2. Although activity across all tumour–drug combinations was modest, defined molecular subgroups and exceptional responders (7.0%) achieved meaningful benefit. To maximize patient benefit, we recommend that off-label precision medicines should be used only within frameworks that systematically evaluate efficacy and toxicity, support biomarker refinement and enable stepwise assessment toward potential future label expansion. These frameworks should prioritize high-confidence targets, early intervention, regulatory-aligned end-points and international collaboration.

DOI: 10.1038/s41586-026-10405-x

Source: https://www.nature.com/articles/s41586-026-10405-x