Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non–Small Cell Lung Cancer

• Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non–small cell lung cancer. JAMA oncology 2018.
• Corresponding Author: Erica L. Carpenter, MBA, PhD, Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 8-104 South Pavilion, 8th Floor, 3400 Civic Center Blvd, Philadelphia, PA 19104 ([email protected]).

IMPORTANCE 重要性

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.

尚未正式评估将基于血浆的循环肿瘤DNA二代测序（NGS）添加至组织NGS以用于非小细胞肺癌（NSCLC）中的靶向突变检测的临床意义。

OBJECTIVE 目标

To determine whether plasma NGS testing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting.

确定血浆NGS测试是否与改进的突变检测和在现实世界临床环境中增强个性化治疗的传递相关。

DESIGN, SETTING, PARTICIPANTS 设计，设置和参与者

This prospective cohort study enrolled 323 patients with metastatic NSCLC who had plasma testing ordered as part of routine clinical 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).

这项前瞻性队列研究纳入了323名转移性非小细胞肺癌患者，他们进行了血浆检测，作为常规临床管理的一部分。血浆NGS使用73基因商业平台进行。患者于2016年4月1日至2018年1月2日在宾夕法尼亚大学医院就诊。该数据库于2018年1月2日被锁定进行随访和分析，中位随访时间为7个月（范围 ，1-21个月）。

MAIN OUTCOMES AND MEASURES 主要结果和措施

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.

用血浆和组织NGS检测到可靶向改变的患者数量; 组织和血浆中检测到的突变的等位基因部分（AF）之间的关联; 以及响应率与靶向突变的血浆AF的关联。

RESULTS 结果

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).

在323例NSCLC患者中（60.1%为女性；中位年龄，65岁[范围，33-93岁]），EGFR、ALK、MET、BRCA1、ROS1、RET、ERBB2或BRAF中共检测到治疗目标突变113例（35.0%）。九十四例患者（29.1%）仅在治疗医生或患者偏好的情况下进行血浆检测。在94例仅进行血浆检测的患者中，31例（33.0%）检测到具有治疗靶向性的突变，因此不需要进行侵袭性活检。在剩下的229名同时患有血浆和组织NGS或不能患有组织NGS的患者中，47名患者（20.5%）仅在组织中检测到治疗性靶向突变，而血浆检测的增加使这一数字增加到82（35.8%）。根据血浆结果接受靶向治疗的42例患者中，36例（85.7%）获得了完全或部分反应或稳定的疾病。血浆靶向突变AF与实体瘤反应深度评价标准无相关性（r=0.121；P=.45）。

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CONCLUSIONS AND RELEVANCE 结论及意义

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.

将血浆NGS检测纳入IV期NSCLC的常规管理表明，可治疗性靶向突变的检测显著增加，并且分子引导治疗的递送得到改善。