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.

尚未正式評估將基於血漿的循環腫瘤DNA二代測序（NGS）添加至組織NGS以用於非小細胞肺癌（NSCLC）中的靶向突變檢測的臨牀意義。

OBJECTIVE 目標

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

確定血漿NGS測試是否與改進的突變檢測和在現實世界臨牀環境中增強個性化治療的傳遞相關。

DESIGN, SETTING, PARTICIPANTS 設計，設置和參與者

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).

這項前瞻性隊列研究納入了323名轉移性非小細胞肺癌患者，他們進行了血漿檢測，作爲常規臨牀管理的一部分。血漿NGS使用73基因商業平臺進行。患者於2016年4月1日至2018年1月2日在賓夕法尼亞大學醫院就診。該數據庫於2018年1月2日被鎖定進行隨訪和分析，中位隨訪時間爲7個月（範圍 ，1-21個月）。

MAIN OUTCOMES AND MEASURES 主要結果和措施

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.

用血漿和組織NGS檢測到可靶向改變的患者數量; 組織和血漿中檢測到的突變的等位基因部分（AF）之間的關聯; 以及響應率與靶向突變的血漿AF的關聯。

RESULTS 結果

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%爲女性；中位年齡，65歲[範圍，33-93歲]），EGFR、ALK、MET、BRCA1、ROS1、RET、ERBB2或BRAF中共檢測到治療目標突變113例（35.0%）。九十四例患者（29.1%）僅在治療醫生或患者偏好的情況下進行血漿檢測。在94例僅進行血漿檢測的患者中，31例（33.0%）檢測到具有治療靶向性的突變，因此不需要進行侵襲性活檢。在剩下的229名同時患有血漿和組織NGS或不能患有組織NGS的患者中，47名患者（20.5%）僅在組織中檢測到治療性靶向突變，而血漿檢測的增加使這一數字增加到82（35.8%）。根據血漿結果接受靶向治療的42例患者中，36例（85.7%）獲得了完全或部分反應或穩定的疾病。血漿靶向突變AF與實體瘤反應深度評價標準無相關性（r=0.121；P=.45）。

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CONCLUSIONS AND RELEVANCE 結論及意義

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.

將血漿NGS檢測納入IV期NSCLC的常規管理表明，可治療性靶向突變的檢測顯著增加，並且分子引導治療的遞送得到改善。