Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.
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纳武单抗用于治疗复发性头颈鳞状细胞癌。
DOI：
10.1056/nejmoa1602252
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发表时间：
2016-11-10
期刊：
影响因子：
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通讯作者：
Gillison ML
中科院分区：
文献类型：
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作者：
Ferris RL;Blumenschein G Jr;Fayette J;Guigay J;Colevas AD;Licitra L;Harrington K;Kasper S;Vokes EE;Even C;Worden F;Saba NF;Iglesias Docampo LC;Haddad R;Rordorf T;Kiyota N;Tahara M;Monga M;Lynch M;Geese WJ;Kopit J;Shaw JW;Gillison ML
铂类化疗后复发或转移的头颈部鳞状细胞癌患者预后极差，治疗选择有限。Nivolumab（一种抗程序性死亡1（PD-1）单克隆抗体）被评估为该疾病的治疗药物。在这项随机、开放标签、3期试验中，我们以2：1的比例将361例复发性头颈部鳞状细胞癌患者分配为接受nivolumab（剂量为3 mg/kg体重）每2周一次或标准单药全身治疗（甲氨蝶呤、多西他赛或西妥昔单抗），这些患者在铂类化疗后6个月内病情进展。主要终点是总生存期。其他终点包括无进展生存期、客观缓解率、安全性和患者报告的生活质量。nivolumab组的中位总生存期为7.5个月（95%置信区间[CI]，5.5至9.1），而接受标准治疗的组为5.1个月（95% CI，4.0至6.0）。nivolumab的总生存期显著长于标准治疗（死亡风险比，0.70; 97.73%CI，0.51至0.96; P = 0.01），nivolumab的1年生存率估计值比标准治疗高约19个百分点（36.0% vs. 16.6%）。nivolumab组的中位无进展生存期为2.0个月（95%CI，1.9至2.1），而标准治疗组为2.3个月（95%CI，1.9至3.1）（疾病进展或死亡的风险比为0.89; 95%CI，0.70至1.13; P = 0.32）。nivolumab治疗6个月时的无进展生存率为19.7%，而标准治疗为9.9%。nivolumab组的应答率为13.3%，而标准治疗组为5.8%。nivolumab组中13.1%的患者发生了3级或4级治疗相关不良事件，而标准治疗组中为35.1%。纳武利尤单抗组的身体、角色和社会功能稳定，而标准治疗组的情况有意义地更糟。在铂难治性复发性头颈部鳞状细胞癌患者中，与标准单药治疗相比，纳武利尤单抗治疗的总生存期更长。（由百时美施贵宝公司资助; CheckMate 141 ClinicalTrials.gov编号，NCT 02105636。）
Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after platinum chemotherapy have a very poor prognosis and limited therapeutic options. Nivolumab, an anti–programmed death 1 (PD-1) monoclonal antibody, was assessed as treatment for this condition. In this randomized, open-label, phase 3 trial, we assigned, in a 2:1 ratio, 361 patients with recurrent squamous-cell carcinoma of the head and neck whose disease had progressed within 6 months after platinum-based chemotherapy to receive nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival. Additional end points included progression-free survival, rate of objective response, safety, and patient-reported quality of life. The median overall survival was 7.5 months (95% confidence interval [CI], 5.5 to 9.1) in the nivolumab group versus 5.1 months (95% CI, 4.0 to 6.0) in the group that received standard therapy. Overall survival was significantly longer with nivolumab than with standard therapy (hazard ratio for death, 0.70; 97.73% CI, 0.51 to 0.96; P = 0.01), and the estimates of the 1-year survival rate were approximately 19 percentage points higher with nivolumab than with standard therapy (36.0% vs. 16.6%). The median progression-free survival was 2.0 months (95% CI, 1.9 to 2.1) with nivolumab versus 2.3 months (95% CI, 1.9 to 3.1) with standard therapy (hazard ratio for disease progression or death, 0.89; 95% CI, 0.70 to 1.13; P = 0.32). The rate of progression-free survival at 6 months was 19.7% with nivolumab versus 9.9% with standard therapy. The response rate was 13.3% in the nivolumab group versus 5.8% in the standard-therapy group. Treatment-related adverse events of grade 3 or 4 occurred in 13.1% of the patients in the nivolumab group versus 35.1% of those in the standard-therapy group. Physical, role, and social functioning was stable in the nivolumab group, whereas it was meaningfully worse in the standard-therapy group. Among patients with platinum-refractory, recurrent squamous-cell carcinoma of the head and neck, treatment with nivolumab resulted in longer overall survival than treatment with standard, single-agent therapy. (Funded by Bristol-Myers Squibb; CheckMate 141 ClinicalTrials.gov number, NCT02105636.)