Dalton W Brian, Forde Patrick M, Kang Hyunseok, Connolly Roisin M, Stearns Vered, Gocke Christopher D, Eshleman James R, Axilbund Jennifer, Petry Dana, Geoghegan Cindy, Wolff Antonio C, Loeb David M, Pratilas Christine A, Meyer Christian F, Christenson Eric S, Slater Shannon A, Ensminger Jennifer, Parsons Heather A, Park Ben H, Lauring Josh
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
Invitae Corporation, San Francisco, CA.
JCO Precis Oncol. 2017;2017. doi: 10.1200/PO.16.00046. Epub 2017 May 31.
Tumor genomic profiling for personalized oncology therapy is being widely applied in clinical practice even as it is being evaluated more formally in clinical trials. Given the complexities of genomic data and its application to clinical use, molecular tumor boards with diverse expertise can provide guidance to oncologists and patients seeking to implement personalized genetically targeted therapy in practice.
A multidisciplinary molecular tumor board reviewed tumor molecular profiling reports from consecutive referrals at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins over a 3-year period. The tumor board weighed evidence for actionability of genomic alterations identified by molecular profiling and provided recommendations including US Food and Drug Administration-approved drug therapy, clinical trials of matched targeted therapy, off-label use of such therapy, and additional tumor or germline genetic testing.
One hundred fifty-five patients were reviewed. Actionable genomic alterations were identified in 132 patients (85%). Off-label therapies were recommended in 37 patients (24%). Eleven patients were treated off-label, and 13 patients were enrolled onto clinical trials of matched targeted therapies. Median progression-free survival of patients treated with matched therapies was 5 months (95% CI, 2.9 months to not reached), and the progression-free survival probability at 6 months was 43%(95% CI, 26% to 71%). Lack of locally available clinical trials was the major limitation on clinical actionability of tumor profiling reports.
The molecular tumor board recommended off-label targeted therapies for a quarter of all patients reviewed. Outcomes were heterogeneous, although 43% of patients receiving genomically matched therapy derived clinical benefit lasting at least 6 months. Until more data become available from precision oncology trials, molecular tumor boards can help guide appropriate use of tumor molecular testing to direct therapy.
肿瘤基因组分析用于个性化肿瘤治疗在临床试验中得到更正式评估的同时,也在临床实践中得到广泛应用。鉴于基因组数据的复杂性及其在临床应用中的情况,具备不同专业知识的分子肿瘤委员会可为寻求在实践中实施个性化基因靶向治疗的肿瘤学家和患者提供指导。
一个多学科分子肿瘤委员会审查了约翰霍普金斯西德尼·金梅尔综合癌症中心在3年期间连续转诊的肿瘤分子分析报告。肿瘤委员会权衡了分子分析确定的基因组改变的可操作性证据,并提供了建议,包括美国食品药品监督管理局批准的药物治疗、匹配靶向治疗的临床试验、此类治疗的非标签使用以及额外的肿瘤或种系基因检测。
共审查了155例患者。132例患者(85%)发现了可操作的基因组改变。37例患者(24%)被推荐进行非标签治疗。11例患者接受了非标签治疗,13例患者参加了匹配靶向治疗的临床试验。接受匹配治疗的患者的无进展生存期中位数为5个月(95%置信区间,2.9个月至未达到),6个月时的无进展生存概率为43%(95%置信区间,26%至71%)。缺乏当地可用的临床试验是肿瘤分析报告临床可操作性的主要限制因素。
分子肿瘤委员会为所有审查患者中的四分之一推荐了非标签靶向治疗。结果存在异质性,尽管43%接受基因组匹配治疗的患者获得了至少持续6个月的临床益处。在从精准肿瘤学试验获得更多数据之前,分子肿瘤委员会可以帮助指导肿瘤分子检测的合理使用以指导治疗。