摘要: 基于分子亚型进行癌症分类的颠覆式发展
全球每4个新增癌症病例中，就有1例是罕见癌症。尽管关于罕见癌症的定义目前还没有形成统一的说法，但它正在引起越来越多的关注。
Rare cancers account for almost a quarter of all new cancers worldwide though there is no universally adopted definition for rare cancers.
以往，癌症一般是按照其所在部位和组织类型来分类。但今天，以分子亚型对癌症进行分类已成为新的趋势。用分子表征方法分类后，往往会使一些常见癌症被重新归类为罕见癌症。
Historically, cancers have been characterized by location and tissue type. Today, however, cancers are increasingly being grouped based on molecular subtypes. This molecular approach to characterization has resulted in the categorization of some common cancers into groups of rare cancers.
基于分子亚型的癌症分类不仅改变了癌症的分类方式，也改变了临床试验中新疗法的研究方式。
对于这一现象，罕见肿瘤领域会因此出现哪些转变?申办方在罕见癌症临床试验中可以通过哪些新方法应对这些转变?在罕见肿瘤领域拥有丰富经验的全球CRO普米尔医药(Premier Research)对此给出了几个关键见解。
The grouping of cancer-based on molecular subtypes has changed not only how cancer is categorized but also how novel therapies are investigated in clinical trials. In this blog post, we explore the changing rare oncology landscape and novel approaches to rare cancer trials.
罕见肿瘤领域关键转变：向精准医疗过渡
传统的癌症治疗方法主要包括手术、放疗和化疗。遗传学和分子分析技术的进步，使得为患者进行个性化定制医疗护理成为新趋势。如今随着精准医疗或个性化医疗的出现，诊疗方式可以针对特定的亚型组患者进行完善，而不必遵循以往“一刀切”式的诊疗模式。
The transition to precision medicine
Traditionally, cancer has been treated by surgery, radiation, and chemotherapy. Advances in genetics and molecular analysis techniques have made more customized patient care possible. Now, with precision or personalized medicine, treatments can be targeted to a subgroup of patients rather than relying on a one-drug-fits-all model.
"广谱”肿瘤疗法代表
随着我们对肿瘤分子特征的认识不断深入，肿瘤的靶向治疗有了巨大飞跃。与此同时，与肿瘤或组织类型无关的"广谱”肿瘤疗法也有了很大发展。这些疗法并非基于肿瘤的部位或组织类型，而是基于分子特征进行治疗。目前，已通过监管部门批准的3种知名"广谱”肿瘤疗法分别为：
• Pembrolizumabin (2017年)-用于高微卫星不稳定性(MSI-H)或错配修复缺陷(dMMR)的肿瘤;
• Larotrectinib(2018年)- 用于NTRK基因融合的肿瘤，不同类型癌症组织学的患者中约0.3%检测到NTRK基因融合;
• Entrectinib(2019年)- 用于NTRK基因融合的肿瘤。
As our understanding of the molecular characteristics of tumors has improved, there has been a tremendous leap forward not only in targeted therapies but also in the development of tumor-or tissue-agnostic treatments. These therapeutics are based not on tumor location or tissue type but on molecular characterization. To date, three tumor agnostic therapies have received regulatory approval:
• Pembrolizumabin 2017 for tumors with microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR)
• Larotrectinib in 2018 for tumors with NTRK gene fusions, which are found in approximately 0.3 percent of patients with varying cancer histologies
• Entrectinib in 2019 for tumors with NTRK gene fusions
推动肿瘤药物无缝开发
在肿瘤学领域，尤其是罕见肿瘤学领域，有越来越多的研究项目已经从传统药物开发途径过渡到无缝药物开发途径。通过新兴的无缝药物开发途径，申办方可以将药理学、治疗性探索研究和验证性研究相结合，以实现加速审批的目的(见图一)。
Pushing the envelope with seamless oncology drug development
In oncology, particularly rare oncology, there are an increasing number of programs that have transitioned from a traditional drug development pathway to a seamless one, where pharmacology, therapeutic exploratory, and confirmatory studies are combined to pursue accelerated approval (see Figure 2).
图1 传统肿瘤药物开发对比无缝肿瘤药物开发
无缝式罕见肿瘤药物开发的关键挑战
•患者群体较少
•患者招募困难
•试验设计因素 - 试验目标、研究群体、亚型分组，以及疗效评估方法等考量因素
•结合基因或生物标记物检测
•生产商 - 加速审批前提下，生产商将面临如何满足营销新需求的挑战
Challenges of a seamless approach to drug development in rare oncology include:
• Small populations –
• Access to patients –
• Study design considerations – When preparing to design a rare oncology study, you will need to clearly define the trial objective, the study population and subgroups, and the methodology used to assess response.
• Incorporation of genetic or biomarker testing
• Manufacturing – With an accelerated program, manufacturing will need to be able to meet the requirements for a marketing application more quickly
由于研发时间有限，确保临床、生产、监管和营销规范之间的一致性，对于通过审批来说也有至关重要的影响。作为一家全球性CRO公司，普米尔医药(Premier Research)提供全方位的产品开发咨询和临床试验服务，可帮助申办方优化罕见肿瘤药物的开发程序。
With shortened timelines, it is also critical to achieve alignment across the clinical, manufacturing, regulatory, and marketing disciplines on how to get to approval. Premier Research offers a full spectrum of product development consulting and clinical development services to help you optimize your rare oncology drug development.
关于普米尔医药(Premier Research)
普米尔医药(Premier Research)是一家临床研究服务提供商，致力于帮助生物科技、专业制药和医疗器械公司将创新理念和突破性科学成果转化为新型医学疗法。无论是制定产品开发战略，缩短临床开发周期，确保受试者接触渠道，提供全球法规咨询，还是提供罕见肿瘤药物开发领域等特定治疗领域的专业知识，普米尔医药致力于在各类医疗条件下，帮助客户解决临床上未被满足的患者需求。
Premier Research, a clinical research company, is dedicated to helping biotech, specialty pharma, and device innovators transform life-changing ideas and breakthrough science into new medical treatments. Whether it's developing product lifecycle strategies, reducing clinical development cycle times, securing access to patients, navigating global regulations, or providing expertise in specific therapeutic areas( like tumor-or tissue-agnostic treatments trails ), Premier Research is committed to helping its customers answer the unmet needs of patients across a broad range of medical conditions.
