纳武利尤单抗对比多西他赛治疗晚期非鳞状非小细胞肺癌
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
作者信息
Borghaei Hossein, Paz-Ares Luis, Horn Leora, Spigel David R, Steins Martin, Ready Neal E, Chow Laura Q, Vokes Everett E, Felip Enriqueta, Holgado Esther, Barlesi Fabrice, Kohlhäufl Martin, Arrieta Oscar, Burgio Marco Angelo, Fayette Jérôme, Lena Hervé, Poddubskaya Elena, Gerber David E, Gettinger Scott N, Rudin Charles M, Rizvi Naiyer, Crinò Lucio, Blumenschein George R, Antonia Scott J, Dorange Cécile, Harbison Christopher T, Graf Finckenstein Friedrich, Brahmer Julie R
机构信息
From the Fox Chase Cancer Center, Philadelphia (H.B.); Hospital Universitario Virgen del Rocio, Seville (L.P.-A.), Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona (E.F.), and Hospital de Madrid, Norte Sanchinarro, Madrid (E.H.) - all in Spain; Vanderbilt-Ingram Cancer Center (L.H.), and Sarah Cannon Research Institute and Tennessee Oncology (D.R.S.) - both in Nashville; Thoraxklinik, Heidelberg University Hospital, Heidelberg (M.S.) and Robert-Bosch-Krankenhaus Stuttgart, Gerlingen (M.K.) - both in Germany; Duke University Medical Center, Durham, NC (N.E.R.); University of Washington, Seattle (L.Q.C.); University of Chicago Medicine and Biological Sciences, Chicago (E.E.V.); Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille (F.B.), Centre Léon Bérard, Lyon (J.F.), and Centre Hospitalier Universitaire de Rennes, Rennes (H.L.) - all in France; Instituto Nacional de Cancerologia, Mexico City (O.A.); Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Forlì-Cesena (M.A.B.), and Ospedale di Perugia, Perugia (L.C.) - both in Italy; N.N. Blokhin Russian Cancer Research Center, Moscow (E.P.); University of Texas Southwestern Medical Center, Dallas (D.E.G.); Yale Comprehensive Cancer Center, New Haven, CT (S.N.G.); Memorial Sloan Kettering Cancer Center, New York (C.M.R., N.R.); University of Texas M.D. Anderson Cancer Center, Houston (G.R.B.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (S.J.A.); Bristol-Myers Squibb, Princeton, NJ (C.D., C.T.H., F.G.F.); and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.R.B.).
出版信息
N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.
BACKGROUND
Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
METHODS
In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.
RESULTS
Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1%, ≥5%, and ≥10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group.
CONCLUSIONS
Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.).
背景
纳武单抗是一种全人源IgG4程序性死亡1（PD-1）免疫检查点抑制剂抗体，可破坏PD-1介导的信号传导，并可能恢复抗肿瘤免疫力。
方法
在这项随机、开放标签的国际3期研究中，我们将在铂类双联化疗期间或之后病情进展的非鳞状非小细胞肺癌（NSCLC）患者分配至接受每2周一次3毫克/千克体重的纳武单抗治疗组，或每3周一次75毫克/平方米体表面积的多西他赛治疗组。主要终点为总生存期。
结果
纳武单抗组的总生存期长于多西他赛组。纳武单抗组292例患者的中位总生存期为12.2个月（95%置信区间[CI]，9.7至15.0），多西他赛组290例患者的中位总生存期为9.4个月（95%CI，8.1至10.7）（死亡风险比，0.73；96%CI，0.59至0.89；P=0.002）。1年时，纳武单抗组的总生存率为51%（95%CI，45至56），多西他赛组为39%（95%CI，33至45）。经过额外随访，18个月时纳武单抗组的总生存率为39%（95%CI，34至45），多西他赛组为23%（95%CI，19至28）。纳武单抗组的缓解率为19%，多西他赛组为12%（P=0.02）。虽然无进展生存期纳武单抗组并不优于多西他赛组（中位分别为2.3个月和4.2个月），但1年时纳武单抗组的无进展生存率高于多西他赛组（分别为19%和8%）。在根据PD-1配体预先设定的肿瘤膜表达水平（≥1%、≥5%和≥10%）定义的亚组中，纳武单抗在所有终点的疗效均优于多西他赛。纳武单抗组10%的患者报告了3级或4级治疗相关不良事件，多西他赛组为54%。
结论
在铂类化疗期间或之后病情进展的晚期非鳞状NSCLC患者中，纳武单抗组的总生存期长于多西他赛组。（由百时美施贵宝公司资助；CheckMate 057临床试验注册号，NCT0*********）
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