Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.
Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.
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DOI：
10.1016/s1470-2045(15)70054-9
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发表时间：
2015-03
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影响因子：
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通讯作者：
Ramalingam SS
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作者：
Rizvi NA;Mazières J;Planchard D;Stinchcombe TE;Dy GK;Antonia SJ;Horn L;Lena H;Minenza E;Mennecier B;Otterson GA;Campos LT;Gandara DR;Levy BP;Nair SG;Zalcman G;Wolf J;Souquet PJ;Baldini E;Cappuzzo F;Chouaid C;Dowlati A;Sanborn R;Lopez-Chavez A;Grohe C;Huber RM;Harbison CT;Baudelet C;Lestini BJ;Ramalingam SS
对多种治疗难治的鳞状非小细胞肺癌患者预后较差。我们评估了nivolumab（一种全人IgG 4 PD-1免疫检查点抑制剂抗体）对晚期难治性鳞状非小细胞肺癌患者的活性。我们在法国、德国、意大利和美国的27个研究中心（学术、医院和私人癌症中心）进行了这项2期单组试验。接受过两次或两次以上既往治疗的患者每2周一次接受静脉内纳武单抗（3 mg/kg），直至进展或不可接受的毒性作用。主要终点是经独立放射学审查委员会评估确认客观缓解的患者比例。我们在分析中纳入了所有接受治疗的患者。本研究注册于ClinicalTrials.gov，编号NCT 01721759。在2012年11月16日至2013年7月22日期间，我们招募并治疗了117例患者。117例患者中有17例（14.5%，95% CI 8.7 - 22.2）经独立放射学审查委员会评估有客观缓解。中位至缓解时间为3.3个月（IQR 2.2 - 4.8），未达到中位缓解持续时间（95% CI 8.31-不适用）;分析时17例缓解中有13例（77%）正在进行中。117例患者中30例（26%）病情稳定（中位持续时间6.0个月，95%CI 4.7 - 10.9）。117例患者中有20例（17%）报告了3-4级治疗相关不良事件，包括：疲劳（117例患者中有5例[4%]）、肺炎（4例[3%]）和腹泻（3例[3%]）。在疾病进展背景下，有2例治疗相关性死亡由肺炎和缺血性卒中引起，发生在有多种合并症的患者中。Nivolumab在既往接受过治疗的晚期难治性鳞状非小细胞肺癌患者中具有临床意义的活性和可管理的安全性特征。这些数据支持在一线和二线治疗的随机、对照、III期研究中评估nivolumab。百时美施贵宝
Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759. Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7–22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2–4·8), and median duration of response was not reached (95% CI 8·31–not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7–10·9). 20 (17%) of 117 patients reported grade 3–4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease. Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment. Bristol-Myers Squibb.