纳武利尤单抗用于复发性头颈部鳞状细胞癌
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck.
作者信息
Ferris Robert L, Blumenschein George, Fayette Jerome, Guigay Joel, Colevas A Dimitrios, Licitra Lisa, Harrington Kevin, Kasper Stefan, Vokes Everett E, Even Caroline, Worden Francis, Saba Nabil F, Iglesias Docampo Lara C, Haddad Robert, Rordorf Tamara, Kiyota Naomi, Tahara Makoto, Monga Manish, Lynch Mark, Geese William J, Kopit Justin, Shaw James W, Gillison Maura L
机构信息
From the University of Pittsburgh Medical Center and Cancer Institute, Pittsburgh (R.L.F.); the Department of Thoracic-Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (G.B.); Centre Leon Berard, Lyon (J.F.), Centre Antoine Lacassagne, Nice (J.G.), and Institut Gustave Roussy, Villejuif (C.E.) - all in France; Stanford Cancer Institute, Stanford, CA (A.D.C.); Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan (L.L.); Institute of Cancer Research-Royal Marsden National Institute for Health Research Biomedical Research Centre, London (K.H.); University Hospital Essen, Essen, Germany (S.K.); University of Chicago, Chicago (E.E.V.); University of Michigan, Ann Arbor (F.W.); Winship Cancer Institute of Emory University, Atlanta (N.F.S.); Hospital Universitario 12 de Octubre, Madrid (L.C.I.D.); Dana-Farber Cancer Institute, Boston (R.H.); Universitätsspital Zurich, Zurich, Switzerland (T.R.); Kobe University Hospital, Kobe (N.K.), and National Cancer Center Hospital East, Kashiwa (M.T.) - both in Japan; Bristol-Myers Squibb, Princeton, NJ (M.M., M.L., W.J.G., J.K., J.W.S.); and Ohio State University, Columbus (M.L.G.).
出版信息
N Engl J Med. 2016 Nov 10;375(19):1856-1867. doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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 .).
背景
铂类化疗后复发或转移性头颈部鳞状细胞癌患者预后极差，治疗选择有限。纳武单抗，一种抗程序性死亡1（PD-1）单克隆抗体，被评估用于治疗这种疾病。
方法
在这项随机、开放标签的3期试验中，我们以2:1的比例将361例铂类化疗后6个月内疾病进展的复发性头颈部鳞状细胞癌患者分配接受每2周一次的纳武单抗（剂量为每公斤体重3毫克）或标准单药全身治疗（甲氨蝶呤、多西他赛或西妥昔单抗）。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。
结果
纳武单抗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）。纳武单抗治疗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），纳武单抗组的1年生存率估计比标准治疗组高约19个百分点（36.0%对16.6%）。纳武单抗组的中位无进展生存期为2.0个月（95%CI，1.9至2.1），标准治疗组为2.3个月（95%CI，1.9至3.1）（疾病进展或死亡风险比，0.89；95%CI，0.70至1.13；P=0.32）。纳武单抗组6个月时的无进展生存率为19.7%，标准治疗组为9.9%。纳武单抗组的缓解率为13.3%，标准治疗组为5.8%。纳武单抗组13.1%的患者发生3级或4级治疗相关不良事件，标准治疗组为35.1%。纳武单抗组的身体、角色和社会功能保持稳定，而标准治疗组则明显恶化。
结论
在铂类难治性复发性头颈部鳞状细胞癌患者中，纳武单抗治疗的总生存期长于标准单药治疗。（由百时美施贵宝公司资助；CheckMate 141临床试验注册号，NCT02105636。）
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