纳武利尤单抗单药用于晚期非小细胞肺癌的一线治疗
Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.
作者信息
Gettinger Scott, Rizvi Naiyer A, Chow Laura Q, Borghaei Hossein, Brahmer Julie, Ready Neal, Gerber David E, Shepherd Frances A, Antonia Scott, Goldman Jonathan W, Juergens Rosalyn A, Laurie Scott A, Nathan Faith E, Shen Yun, Harbison Christopher T, Hellmann Matthew D
机构信息
Scott Gettinger, Yale Cancer Center, New Haven, CT; Naiyer A. Rizvi and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; Laura Q. Chow, University of Washington, Seattle, WA; Hossein Borghaei, Fox Chase Cancer Center, Philadelphia, PA; Julie Brahmer, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Neal Ready, Duke University Medical Center, Durham, NC; David E. Gerber, University of Texas Southwestern Medical Center, Dallas, TX; Frances A. Shepherd, Princess Margaret Cancer Centre, Toronto; Rosalyn A. Juergens, Juravinski Cancer Centre at McMaster University, Hamilton; Scott A. Laurie, Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada; Scott Antonia, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Jonathan W. Goldman, University of California, Los Angeles, Los Angeles, CA; and Faith E. Nathan, Yun Shen, and Christopher T. Harbison, Bristol-Myers Squibb, Princeton, NJ.
出版信息
J Clin Oncol. 2016 Sep 1;34(25):2980-7. doi: 10.1200/JCO.2016.66.9929. Epub 2016 Jun 27.
PURPOSE
Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial.
METHODS
Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point.
RESULTS
Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD-ligand 1 expression and 14% (two of 14) in patients with no PD-ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively.
CONCLUSION
First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.
目的
纳武利尤单抗是一种程序性死亡受体1（PD-1）免疫检查点抑制剂抗体，已证实在既往接受过治疗的晚期非小细胞肺癌（NSCLC）中，其生存期优于多西他赛。在I期多队列Checkmate 012试验中评估了纳武利尤单抗用于晚期NSCLC的一线单药治疗。
方法
52例患者每2周静脉注射纳武利尤单抗3 mg/kg，直至疾病进展或出现不可接受的毒性；根据方案允许进展后治疗。主要目标是评估安全性；次要目标包括客观缓解率（ORR）和24周无进展生存期（PFS）率；总生存期（OS）是一个探索性终点。
结果
71%的患者发生了任何级别的治疗相关不良事件（AE），最常见的有：疲劳（29%）、皮疹（19%）、恶心（14%）、腹泻（12%）、瘙痒（12%）和关节痛（10%）。10例患者（19%）报告了3至4级治疗相关AE；3级皮疹是唯一发生在不止1例患者中的3至4级事件（n = 2；4%）。6例患者（12%）因治疗相关AE停药。确认的ORR为23%（52例中的12例），包括4例持续完全缓解。12例缓解中有9例（75%）在首次肿瘤评估时（第11周）出现；在数据锁定时，8例（67%）仍在持续缓解（范围为5.3+至25.8+个月）。肿瘤PD-配体1表达程度不同的患者中，ORR在有任何程度表达的患者中为28%（32例中的9例），在无PD-配体1表达的患者中为14%（14例中的2例）。中位PFS为3.6个月，24周PFS率为41%（95%CI，27至54）。中位OS为19.4个月，1年和18个月的OS率分别为73%（95%CI，59至83）和57%（95%CI，42至70）。
结论
纳武利尤单抗一线单药治疗在一线晚期NSCLC中显示出可耐受的安全性和持久缓解。
Zotero 插件