PD-L1 Assessment for Targeted Therapy Testing in Cancer: Urgent Need For Realistic Economic and Practice Expectations.
PD-L1 Assessment for Targeted Therapy Testing in Cancer: Urgent Need For Realistic Economic and Practice Expectations.
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癌症靶向治疗测试的 PD-L1 评估：迫切需要现实的经济和实践期望。
DOI：
10.1097/pai.0000000000000472
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Taylor,CliveR
中科院分区：
文献类型：
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作者：
Yaziji,Hadi;Taylor,CliveR
近年来，以单克隆抗体和小分子抑制剂形式出现的新一代治疗剂的爆炸式增长，这些药物被设计成靶向癌细胞上或癌细胞中表达的特异性蛋白质受体，因此称为靶向治疗剂。首先开发的此类药物是曲妥珠单抗[抗HER 2-食品和药物管理局（FDA）1998年批准]和Rituxumab（抗CD 20-FDA 2006年批准）。快进到2016年，几十种类似的药物不仅可用于癌症的靶向治疗，还可用于慢性疾病，还有更多的产品正在审批中。其中一些药物已成为“一线”治疗选择，而另一些则用作新辅助治疗，代替（或补充）标准的“老式”化疗。例如，EGFR小分子抑制剂正逐渐成为非小细胞肺癌（NSCLC）的一线靶向治疗药物，这一切都令人兴奋，但为了使这些靶向治疗药物发挥最大疗效，准确检测改变的基因或“过表达”的膜蛋白受体至关重要。目前的方法包括组织提取物的分子分析和基于载玻片的荧光原位杂交或免疫组织化学（IHC）检测。1，2在这种情况下，这些测试属于伴随（或补充）诊断的一般类别。在美国，政府监管机构，特别是FDA，已经建立了在联合临床试验中与相应的靶向治疗共同开发“伴随诊断”的先例。在这一过程中，FDA给出了体外诊断（IVD）伴随诊断的工作定义，包括某些内在标准：“它提供了安全有效使用相应治疗产品所必需的信息”，其用途“在诊断器械和相应治疗药物的标签使用说明书中规定”。3，4因此，必须使用伴随药物。在一些共同开发试验中，“测试”不符合应答者与无应答者分类的统计阈值，此类测试被称为补充诊断;可能建议但不要求使用。
Recent years have witnessed the explosion of a new generation of therapeutic agents in the form of monoclonal antibodies and small molecule inhibitors that are designed to target specific protein receptors expressed on, or in, cancer cells—hence the term targeted therapy agents. Among the first to be developed of such agents are Trastuzumab [anti-HER2—Food and Drug Administration (FDA) approved 1998] and Rituxumab (anti-CD20—FDA approved 2006). Fast forward to 2016, and several dozen similar agents are available not only for the targeted therapy of cancer but for chronic diseases as well, 1 with many more products in the approval pipeline. 2 Some of these agents have become the “first-line” therapy choice, whereas others are used as neoadjuvant therapy, instead of (or in addition to) the standard “old-fashioned” chemotherapy. For example, EGFR small molecular inhibitors are making their way to become the first-line treatment targeted therapy in non–smallcell lung cancer (NSCLC).All this is exciting, but in order for these targeted therapy agents to achieve maximum effectiveness, accurate detection of the altered gene or “overexpressed” membrane protein receptor is of paramount importance. Current methods include molecular analysis of tissue extracts and slide-based fluorescence in situ hybridization or immunohistochemistry (IHC) testing. 1, 2 In this context these tests fall under the general rubric of companion (or complementary) diagnostics. In the United States, governmental regulatory agencies, in particular the FDA, have established the precedent for codevelopment of the “companion diagnostic” in joint clinical trials with the corresponding targeted therapy. In this process a working definition of an in vitro diagnostic (IVD) companion diagnostic emerged from the FDA, including certain intrinsic criteria:“it provides information that is essential for the safe and effective use of a corresponding therapeutic product,” and its use is “stipulated in the instructions for use in the labeling of both the diagnostic device and the corresponding therapeutic agent.” 3, 4 Hence, use is mandated in order to administer the companion drug. In some codevelopment trials the “test” did not meet the statistical thresholds for classification of responders versus nonresponders, and such tests have been termed complementary diagnostics; their use may be recommended but is not required.