Coyne Geraldine O'Sullivan, Takebe Naoko, Chen Alice P
Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Curr Probl Cancer. 2017 May-Jun;41(3):182-193. doi: 10.1016/j.currproblcancer.2017.02.001. Epub 2017 Feb 11.
"Precision" trials, using rationally incorporated biomarker targets and molecularly selective anticancer agents, have become of great interest to both patients and their physicians. In the endeavor to test the cornerstone premise of precision oncotherapy, that is, determining if modulating a specific molecular aberration in a patient's tumor with a correspondingly specific therapeutic agent improves clinical outcomes, the design of clinical trials with embedded genomic characterization platforms which guide therapy are an increasing challenge. The National Cancer Institute Precision Medicine Initiative is an unprecedented large interdisciplinary collaborative effort to conceptualize and test the feasibility of trials incorporating sequencing platforms and large-scale bioinformatics processing that are not currently uniformly available to patients. National Cancer Institute-Molecular Profiling-based Assignment of Cancer Therapy and National Cancer Institute-Molecular Analysis for Therapy Choice are 2 genomic to phenotypic trials under this National Cancer Institute initiative, where treatment is selected according to predetermined genetic alterations detected using next-generation sequencing technology across a broad range of tumor types. In this article, we discuss the objectives and trial designs that have enabled the public-private partnerships required to complete the scale of both trials, as well as interim trial updates and strategic considerations that have driven data analysis and targeted therapy assignment, with the intent of elucidating further the benefits of this treatment approach for patients.
“精准”试验，即使用合理纳入的生物标志物靶点和分子选择性抗癌药物，已引起患者及其医生的极大兴趣。在努力检验精准肿瘤治疗的基石前提，即确定用相应的特异性治疗药物调节患者肿瘤中的特定分子异常是否能改善临床结果时，设计带有指导治疗的嵌入式基因组特征分析平台的临床试验面临着越来越大的挑战。美国国立癌症研究所精准医学计划是一项前所未有的大型跨学科合作努力，旨在构思并测试纳入测序平台和大规模生物信息学处理的试验的可行性，而目前患者无法普遍获得这些资源。美国国立癌症研究所基于分子谱分析的癌症治疗分配和美国国立癌症研究所治疗选择分子分析是美国国立癌症研究所这一计划下的两项从基因组到表型的试验，在这些试验中，根据使用下一代测序技术在广泛肿瘤类型中检测到的预先确定的基因改变来选择治疗方法。在本文中，我们讨论了实现完成两项试验规模所需的公私合作关系的目标和试验设计，以及推动数据分析和靶向治疗分配的中期试验更新和战略考量，旨在进一步阐明这种治疗方法对患者的益处。
