Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular-screening program was intended to route participants to different candidate drugs in trials based on clinical-sequencing reports. In this screening program, we used a custom target-enrichment panel consisting of cancer-related genes to interrogate single-nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions. From August 2014 through April 2015, 654 patients consented to participate in the program at Samsung Medical Center. Of these patients, 588 passed the quality control process for the 381-gene cancer-panel test, and 418 patients were included in the final analysis as being eligible for any anticancer treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the 418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker-selected clinical trial, and 184 (44%) patients harbored at least one genomic alteration that was potentially targetable. This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.
Implications for practice: This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase.
摘要
难治性癌症患者中可诉性突变（actionable mutation）的分子表达谱有助于实现”精准医疗”（根据基因组表达谱指导个体化疗法）。分子筛选计划拟根据临床测序报告将试验参与者分配至不同的候选药物组。本筛选计划使用了包括癌症相关基因的定制靶向富集面板, 以分析单核苷酸变体、插入和删除, 拷贝数目变异（CNV）和基因融合子集。2014年8月至2015年4月期间, 654名患者表示同意参与在三星医疗中心开展的筛选项目。在这些患者中, 588名通过了381个基因癌症面板检测的质控过程, 418名患者由于适合使用任何抗癌治疗被纳入最终分析（127名胃癌患者, 122名结直肠癌患者, 62名胰腺/胆道癌患者, 67名肉瘤/其它癌症患者, 40名泌尿生殖肿瘤患者）。在这418名患者中, 55名（12%）有使其适合参加选定生物标志物临床试验的生物标志物, 184名（44%）有至少一种潜在靶向的基因组变异。本研究证实, 基于面板的测序计划增加了选定生物标志物临床试验中转移性肿瘤患者的入组率。由于选定生物标志物试验增多, 预计被分配到匹配试验的患者百分比会升高。
对临床实践的提示：本研究证实, 基于面板的测序计划增加了选定生物标志物临床试验中转移性肿瘤患者的入组率。由于选定生物标志物试验增多, 预计被分配到匹配试验的患者百分比会升高。
Trial registration: ClinicalTrials.gov NCT02141152.
Keywords: Clinical trials; Metastatic cancer; Molecular screening; Next‐generation sequencing.
© AlphaMed Press 2017.