Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.
Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.
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DOI：
10.1200/po.19.00087
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发表时间：
2019-01-01
影响因子：
4.6
通讯作者：
Lin, Nancy U
中科院分区：
文献类型：
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作者：
Exman, Pedro;Garrido-Castro, Ana C;Lin, Nancy U
目的：在为小亚组设计的基于分子的试验中招募患者时，综合基因组图谱的产量尚未得到充分评估。我们评估了纳入临床试验的可能性，该试验需要根据我们研究所范围内的基因组肿瘤谱确定特定的基因组变化。患者和方法：使用2011年至2017年间接受治疗的转移性乳腺癌患者的存档组织样本的基因组图谱，我们评估了系统基因组表征对正在进行的II期试验（ClinicalTrials.gov标识符：NCT01670877）入组的影响。我们的主要目的是描述通过我们的机构基因组小组（OncoMap或OncoPanel）确定的符合ERBB2突变的患者参加试验的比例。次要目标包括从测试结果到试验注册的中位时间、ERBB2突变谱的描述和生存。使用Fisher精确检验计算关联。结果：我们共确定了1045例没有ERBB2扩增的转移性乳腺癌患者，他们有可用的基因组检测结果。其中，42名患者被发现有ERBB2突变，19名患者（1.8%）因存在激活突变而符合试验条件，其中18名患者通过OncoPanel检测确定。58%的潜在符合条件的患者进行了接触，33.3%的符合条件的患者在OncoPanel测试的指导下参加了试验。结论：超过一半的符合条件的患者参与了试验，值得注意的是，其中三分之一的患者入组了NCT01670877。我们的数据说明了在常规临床实践中招募罕见亚群患者进行试验的能力，并强调需要这些广泛的方法来有效地支持这些研究的成功。
PURPOSE: The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling.PATIENTS AND METHODS: Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877). Our primary aim was to describe the proportion of patients with a qualifying ERBB2 mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of ERBB2 mutations, and survival. Associations were calculated using Fisher's exact test.RESULTS: We identified a total of 1,045 patients with metastatic breast cancer without ERBB2 amplification who had available genomic testing results. Of these, 42 patients were found to have ERBB2 mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing.CONCLUSION: More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.