MASTER KEY Project: Powering Clinical Development for Rare Cancers Through a Platform Trial
MASTER KEY Project: Powering Clinical Development for Rare Cancers Through a Platform Trial
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DOI：
10.1002/cpt.1817
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发表时间：
2020-04-07
影响因子：
6.7
通讯作者：
Fujiwara, Yasuhiro
中科院分区：
文献类型：
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作者：
Okuma, Hitomi S.;Yonemori, Kan;Fujiwara, Yasuhiro
对于罕见的癌症，建立标准疗法的挑战比对主要癌症的挑战更大，需要有效的方法。万能钥匙项目是一项总部设在日本的多中心研究，包括两个主要部分：前瞻性注册研究和多个临床试验。目标是晚期罕见癌症、原发原因不明的癌症以及常见癌症中罕见组织亚型的癌症。注册研究积累了高度可靠的连续数据，可用于未来的药物开发。多项试验同时进行，目标要么是特定的生物标记物，要么是感兴趣的罕见肿瘤类型。这里提供的来自注册部分的第一个临时数据集显示了遗传异常的流行率、应答率、存活率和临床试验注册率。从2017年5月至2019年4月，560名患者(平均年龄=53岁)参加了该项目。常见的癌症类型包括软组织肉瘤、神经内分泌肿瘤和中枢神经系统肿瘤。在528名有可评估数据的患者中，69%(364/528)接受了下一代测序测试，其中48%(176/364)存在“可操作”的改变。71名患者(13%)参加了一项临床试验，累积率为3.94人/月。对生物标志物导向或非生物标志物导向的治疗生存率进行描述性分析。该项目有望加快罕见癌症治疗方法的开发，并表明综合平台试验是一种有利的战略。
For rare cancers, challenges in establishing standard therapies are greater than those for major cancers, and effective methods are needed. MASTER KEY Project is a multicenter study based in Japan, with two main parts: prospective registry study and multiple clinical trials. Advanced rare cancers, cancers of unknown primary origin, and those with rare tissue subtypes of common cancers are targeted. The registry study accumulates highly reliable consecutive data that can be used for future drug development. The multiple trials are conducted simultaneously, targeting either a specific biomarker or a rare tumor type of interest. The first interim data set from the registry part presented here shows the prevalence of genetic abnormalities, response rates, survival rates, and clinical trial enrollment rates. From May 2017 to April 2019, 560 patients (mean age = 53) were enrolled in the project. Frequent cancer types included soft tissue sarcomas, neuroendocrine tumors, and central nervous system tumors. Among the 528 patients with assessable data, 69% (364/528) had next-generation sequencing tests, with 48% (176/364) harboring an "actionable" alteration. Seventy-one (13%) patients have been enrolled in one of the clinical trials, with an accrual rate of 3.94 patients/month. A descriptive analysis of biomarker-directed or non-biomarker-directed treatment survival was performed. This project is expected to accelerate development of treatments for rare cancers and show that comprehensive platform trials are an advantageous strategy.