PO.CL09.03 · 临床研究
确定综合分子检测在晚期癌症中的获益：BostonGene与Exigent基因组洞察（BEGIN）研究
Determining the benefit of comprehensive molecular testing in advanced cancers: BostonGene and Exigent Genomic INsight (BEGIN) study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：越来越多的证据表明，综合基因组和分子检测有可能实现更精准、有效和个体化的癌症治疗。然而，在试验之外，检测并不一致，实践中的采用也很有限。BostonGene与Exigent基因组洞察研究（BEGIN；NCT06272864）是一项正在进行的、前瞻性、多中心研究，评估整合DNA/RNA综合基因组分析（CGP）在社区环境中的临床实用性和可操作性。使用多模态Tumor Portrait检测，对晚期肿瘤患者进行了CLIA认证的全外显子组测序（WES）、全转录组RNA-seq和肿瘤微环境（TME）分型。
方法：我们在Exigent研究网络内的六个社区实践点，征得同意并前瞻性纳入了患有晚期乳腺癌、非小细胞肺癌（NSCLC）、黑色素瘤或肉瘤的成年患者。所有患者均使用Tumor Portrait检测进行了WES、RNA-seq和TME分析。可操作发现定义为与FDA批准或NCCN®推荐疗法的关联，或符合生物标志物匹配临床试验的资格。可靶向分子（如ERBB2 [HER2]、CD274 [PD-L1]）的RNA-seq表达也被归类为可操作。未报告驱动突变的缺失。在6个月和12个月时收集人口统计学、既往治疗、治疗决策和临床结局。
结果：我们分析了156例患者（乳腺癌，n = 87；NSCLC，n = 41；黑色素瘤，n = 21；肉瘤，n = 7），这些患者在报告交付后有≥6个月的随访。综合检测的中位周转时间为8个工作日。在221例筛查患者中，样本失败率为14.4%（32/221）。在93%的患者（145/156）中识别出可操作发现，其中约10%（15/145）归因于RNA-seq，而仅DNA检测会遗漏。按肿瘤类型划分的可操作发现率为：乳腺癌95.4%；NSCLC 87.8%；黑色素瘤95.2%；肉瘤71.4%。在156例患者中的71例（45.5%）中识别出至少一个NCCN®/FDA关联的CGP生物标志物。138例患者有检测后随访；中位随访时间为6个月，其中68/156（43.5%）随访≥12个月。RNA或DNA发现通过启动基因组匹配的全身治疗和/或转诊至生物标志物筛选的试验，直接指导或改变了10%患者的临床进程。
结论：整合DNA/RNA CGP在93%的患者中识别出可操作发现，其中10%的可操作发现由RNA表达识别，而DNA检测会遗漏。本研究展示了外显子组-转录组联合分析在社区实践中用于精准肿瘤学的临床实用性，直接影响患者的治疗选择。BEGIN的持续随访将评估其对患者相关结局的影响，包括无进展生存和总生存，以及临床试验入组情况。
查看英文原文 English abstract
Introduction: Growing evidence suggests that comprehensive genomic and molecular testing has the potential to enable more precise, effective, and individualized cancer care. However, outside of trials, testing is inconsistent, and adoption into practice is limited. The BostonGene and Exigent Genomic INsight Study (BEGIN; NCT06272864) is an ongoing, prospective, multi-site study evaluating the clinical utility and actionability of integrated DNA/RNA comprehensive genomic profiling (CGP) in community settings. Using the multimodal Tumor Portrait test, CLIA-certified whole-exome sequencing (WES), whole-transcriptome RNA-seq, and tumor microenvironment (TME) subtyping were performed in pts. with advanced tumors.
Methods: We consented and prospectively enrolled adult pts. with advanced breast cancer, non-small cell lung cancer (NSCLC), melanoma, or sarcoma at six community practice sites within the Exigent Research Network. All pts. underwent WES, RNA-seq, and TME profiling using the Tumor Portrait test. Actionable findings were defined by links to FDA-approved or NCCN®-recommended therapies or eligibility for biomarker-matched clinical trials. RNA-seq expression of targetable molecules (e.g., ERBB2 [HER2], CD274 [PD-L1]) was also classified as actionable. Absence of driver mutations were not reported. Demographics, prior therapy, treatment decisions, and clinical outcomes were collected at 6 and 12 mos.
Results: We analyzed 156 pts. (breast, n = 87; NSCLC, n = 41; melanoma, n = 21; sarcoma, n = 7) with ≥6 mos. of follow-up after report delivery. The median turn around time for comprehensive testing was 8 business days. Out of 221 screened pts., the sample failure rate was 14.4% (32/221). Actionable findings were identified in 93% of pts. (145/156), with ~10% (15/145) attributable to RNA-seq and missed by DNA-only testing. Actionable finding rates by tumor type were: breast, 95.4%; NSCLC, 87.8%; melanoma, 95.2%; and sarcoma, 71.4%. At least one NCCN®/FDA-linked CGP biomarker was identified in 71 of 156 pts. (45.5%). Post-testing follow-up was available for 138 pts.; median follow-up was 6 mos., with 68/156 (43.5%) at ≥12 mos. RNA or DNA findings directly informed or altered the clinical course through the initiation of genomically matched systemic therapy and/or referral to biomarker-selected trials in 10% of pts.
Conclusions: Integrated DNA/RNA CGP identified actionable findings in 93% of pts., with 10% of actionable findings being identified by RNA expression that were missed by DNA testing. This study demonstrates the clinical utility of combined exome-transcriptome profiling for precision oncology in community practice, which directly impacts patients' therapeutic options. Continued follow-up with BEGIN will assess the impact on patient-related outcomes, including progression-free and overall survival, as well as clinical trial accrual.
利益披露 Disclosure
S. Blau,
Northwest Medical Specialties Employment.
Exigent Research g., Board of Directors, non-salaried role).
ONCare Alliance g., Board of Directors, non-salaried role).
All4Cure g., Board of Directors, non-salaried role).
P1 Trials g., Board of Directors, non-salaried role).
K. Sanchez,
New Mexico Cancer Center Employment.
Exigent g., Board of Directors, non-salaried role).
E. Schaefer,
Highlands Oncology Group Employment.
J. A. Peguero,
Exigent g., Board of Directors, non-salaried role).
Oncology Consultants Employment.
P. Zito,
Oklahoma Cancer Specialists and Research Institute Employment.
Exigent g., Board of Directors, non-salaried role).
D. Kodali,
Stockton Hematology Oncology Medical Group Employment.
A. Tarasov,
BostonGene Corporation Employment.
R. Carter,
BostonGene Corporation Employment, Stock Option.
K. Hendricks,
BostonGene Corporation Employment, Stock Option.
A. Love,
BostonGene Corporation Employment, Stock Option.
L. Kontselidze,
BostonGene Corporation Employment.
P. Turova,
BostonGene Corporation Employment, Stock Option.
V. Smirnov,
BostonGene Corporation Employment, Stock Option.
A. Ogloblina,
BostonGene Corporation Employment, Stock Option.
K. Rumyantsev,
BostonGene Corporation Employment.
N. Makani,
BostonGene Corporation Employment.
Comprehensive Hematology Oncology Employment.
A. Bagaev,
BostonGene Corporation Employment, g., Board of Directors, non-salaried role), Stock Option, Patent.
N. Fowler,
BostonGene Corporation Employment, g., Board of Directors, non-salaried role), Stock Option.
CelGene ).
Roche ).
Gilead ).