On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker Actionability in 439 Patients
On the Road to Precision Cancer Medicine: Analysis of Genomic Biomarker Actionability in 439 Patients
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DOI：
10.1158/1535-7163.mct-14-1061
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发表时间：
2015-06-01
影响因子：
5.7
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
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作者：
Schwaederle, Maria;Daniels, Gregory A.;Kurzrock, Razelle
尽管越来越多地使用分子诊断，在何种程度上，患者谁拥有这些测试潜在的可操作的畸变是不清楚的。我们回顾性分析了439例患有不同癌症的患者，他们进行了下一代测序（主要是236个基因组）。从分子诊断报告中提取与识别的分子改变相关的数据以及相关的治疗建议（适应症内或适应症外，或实验性）。大多数患者（420/439; 96%）至少有一个分子改变：确定了1，813个改变（在207个不同的基因中）[大多数是突变（62%）或扩增（29%）]。三种最常见的基因异常是TP 53（44%），KRAS（16%）和PIK 3CA（12%）。每例患者的中位变异数为3（范围，0-16）。19例患者（4%）没有改变; 48例患者（11%）只有一个改变; 372例患者有两个或两个以上的异常（85%）。每例患者潜在可采取措施的异常的中位数为2（范围，0-8）。大多数患者（393/439; 90%）至少有一个潜在的可操作的改变，在所有这些情况下，畸变至少可以通过临床试验中的实验药物靶向。共有307例患者（70%）发生了可使用获批药物的变化，但只有89例患者（20%）的药物获批用于其疾病（按标签使用）。下一代测序在我们90%的患者中发现了理论上可行的畸变。然而，许多药物是实验性的，或者需要标签外使用。需要制定策略，解决携带潜在可操作突变的患者的药物获取问题。（C）2015年AACR。
Despite the increased use of molecular diagnostics, the extent to which patients who have these tests harbor potentially actionable aberrations is unclear. We retrospectively reviewed 439 patients with diverse cancers, for whom next-generation sequencing (mostly 236-gene panel) had been performed. Data pertaining to the molecular alterations identified, as well as associated treatment suggestions (on-or off-label, or experimental), were extracted from molecular diagnostic reports. Most patients (420/439; 96%) had at least one molecular alteration: 1,813 alterations (in 207 distinct genes) were identified [the majority being mutations (62%) or amplifications (29%)]. The three most common gene abnormalities were TP53 (44%), KRAS (16%), and PIK3CA (12%). The median number of alterations per patient was 3 (range, 0-16). Nineteen patients (4%) had no alterations; 48 patients (11%) had only one alteration; and 372 patients had two or more abnormalities (85%). The median number of potentially actionable anomalies per patient was 2 (range, 0-8). Most patients (393/439; 90%) had at least one potentially actionable alteration, and in all these cases the aberration could at least be targeted by an experimental drug in a clinical trial. A total of 307 patients (70%) had an alteration that was actionable with an approved drug, but in only 89 patients (20%) was the drug approved for their disease (on-label). Next-generation sequencing identified theoretically actionable aberrations in 90% of our patients. Many of the drugs are, however, experimental or would require off-label use. Strategies to address drug access for patients harboring potentially actionable mutations are needed. (C)2015 AACR.