Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer
Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer
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DOI：
10.1001/jamaoncol.2018.4305
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发表时间：
2019-02-01
期刊：
影响因子：
28.4
通讯作者：
Carpenter, Erica L.
中科院分区：
文献类型：
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作者：
Aggarwal, Charu;Thompson, Jeffrey C.;Carpenter, Erica L.
将基于血浆的循环肿瘤DNA下一代测序(NGS)添加到组织NGS中用于非小细胞肺癌(NSCLC)靶向突变检测的临床意义尚未得到正式评估。目的在真实的临床环境中确定血浆NGS检测是否与改进的突变检测和增强个性化治疗的提供相关。设计、设置和参与者这项前瞻性队列研究招募了323名转移性NSCLC患者，他们的血浆检测被安排为常规临床治疗的一部分。采用73基因商业平台进行血浆NGS检测。从2016年4月1日到2018年1月2日，患者在宾夕法尼亚大学医院登记。数据库于2018年1月2日锁定以进行跟踪和分析，平均随访时间为7个月(范围为1-21个月)。MAIN结果和测量在血浆和组织NGS中检测到的靶向性改变的患者数量；在组织和血浆中检测到的突变的等位基因分数(AFs)之间的关联；以及应答率与靶向突变的血浆AF的关联。中位年龄65岁[范围33-93岁]，总共113人(35.0%)在EGFR、ALK、MET、BRCA1、ROS1、RET、ERBB2或BRAF中检测到治疗靶向突变。94名患者(29.1%)只有在治疗医生或患者偏好的情况下才进行血浆测试。在94例单独进行血浆检测的患者中，31例(33.0%)检测到了治疗靶向突变，因此不需要侵入性活组织检查。在其余229名同时患有血浆和组织NGS或无法获得组织NGS的患者中，47名患者(20.5%)仅在组织中检测到具有治疗靶向性的突变，而增加血浆检测使这一数字增加到82名(35.8%)。根据血浆结果接受靶向治疗的42例患者中，36例(85.7%)完全或部分缓解或病情稳定。血浆靶向突变AF与实体瘤反应深度评估标准无相关性(r=-0.121；P=.45)。结论将血浆NGS检测与IV期非小细胞肺癌常规治疗相结合，显著增加了治疗靶向突变的检测，并改善了分子导向治疗的实施。
IMPORTANCE The clinical implications of adding plasma-based circulating tumor DNA next-generation sequencing (NGS) to tissue NGS for targetable mutation detection in non-small cell lung cancer (NSCLC) have not been formally assessed.OBJECTIVE To determine whether plasma NGS testing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting.DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study enrolled 323 patients with metastatic NSCLC who had plasma testing ordered as part of routine dinical management. Plasma NGS was performed using a 73-gene commercial platform. Patients were enrolled at the Hospital of the University of Pennsylvania from April 1, 2016, through January 2, 2018. The database was locked for follow-up and analyses on January 2, 2018, with a median follow-up of 7 months (range, 1-21 months).MAIN OUTCOMES AND MEASURES The number of patients with targetable alterations detected with plasma and tissue NGS; the association between the allele fractions (AFs) of mutations detected in tissue and plasma; and the association of response rate with the plasma AF of the targeted mutations.RESULTS Among the 323 patients with NSCLC (60.1% female; median age, 65 years [range, 33-93 years]), therapeutically targetable mutations were detected in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2, or BRAF for 113 (35.0%) overall. Ninety-four patients (29.1%) had plasma testing only at the discretion of the treating physician or patient preference. Among the 94 patients with plasma testing alone, 31(33.0%) had a therapeutically targetable mutation detected, thus obviating the need for an invasive biopsy. Among the remaining 229 patients who had concurrent plasma and tissue NGS or were unable to have tissue NGS, a therapeutically targetable mutation was detected in tissue alone for 47 patients (20.5%), whereas the addition of plasma testing increased this number to 82 (35.8%). Thirty-six of 42 patients (85.7%) who received a targeted therapy based on the plasma result achieved a complete or a partial response or stable disease. The plasma-based targeted mutation AF had no correlation with depth of Response Evaluation Criteria in Solid Tumors response (r = -0.121; P = .45).CONCLUSIONS AND RELEVANCE Integration of plasma NGS testing into the routine management of stage IV NSCLC demonstrates a marked increase of the detection of therapeutically targetable mutations and improved delivery of molecularly guided therapy.