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帕博利珠单抗与化疗治疗PD-L1阳性非小细胞肺癌的比较研究
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer


Martin Reck ... 肿瘤 呼吸系统疾病 • 2016.11.10
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PD-1抑制剂改变非小细胞肺癌一线治疗格局

 

梁文华,何建行*

广州医科大学附属第一医院胸部肿瘤科

* 通讯作者

 

2016年10月,KEYNOTE-024结果正式在《新英格兰医学杂志》公布1,首次证实PD-1单抗在PD-L1高表达的非小细胞肺癌(NSCLC)的一线治疗中,疗效完胜标准的含铂双药化疗的研究:PD-1单抗pembrolizumab较化疗组延长了4个月的无进展生存期,并显示出更高的客观缓解率(45%对28%),以及更持续的缓解时间和更低的毒副作用。

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摘要


背景

帕博利珠单抗是程序性死亡受体-1(PD-1)的人源化单克隆抗体,在进展期非小细胞肺癌(NSCLC)中具有抗肿瘤活性,并且在表达程序性死亡受体配体1(PD-L1)的肿瘤中具有更高的活性。

 

方法

在这项开放性、三期临床试验中,我们随机将305例至少有50%肿瘤细胞表达PD-L1,并且未携带表皮生长因子受体基因的增敏突变或间变性淋巴瘤激酶基因易位的未经治疗的进展期NSCLC患者分配到帕博利珠单抗组(固定剂量200 mg,每3周一次)或者研究者选择的以铂类为基础的化疗组;化疗组患者出现疾病进展后,可以跨线至帕博利珠单抗组。主要终点,无进展生存期,是由盲法、独立的、中心影像学判读进行评估。次要终点包括总生存期、客观有效率以及安全性。

 

结果

帕博利珠单抗组中位无进展生存期是10.3个月(95%可信区间[CI],6.7至尚未达到),化疗组为6.0个月(95% CI,4.2~6.2)(疾病进展或死亡的风险比为0.50;95% CI,0.37~0.68;P<0.001)。帕博利珠单抗组的6个月估计总生存率为80.2%,而化疗组为72.4%(死亡的风险比为0.60;95% CI,0.41~0.89;P=0.005)。帕博利珠单抗组的有效率高于化疗组(44.8%对27.8%),中位缓解时间更长(尚未达到[范围,1.9+至14.5+个月])对6.3个月[范围,2.1+至12.6+个月]),此外,各个级别的治疗相关不良事件发生率更低(发生率73.4%对90.0%),并且3级、4级或5级不良事件的发生率也较低(26.6%对53.3%)。

 

结论

对于至少50%肿瘤细胞表达PD-L1的进展期NSCLC患者而言,与以铂类为基础的化疗相比,帕博利珠单抗治疗可显著延长无进展生存期和总生存期,并且不良事件发生率较低(由默克[Merck]公司资助;KEYNOTE-024在ClinicalTrials.gov注册号为NCT02142738)。





作者信息

Martin Reck, M.D., Ph.D., Delvys Rodríguez-Abreu, M.D., Andrew G. Robinson, M.D., Rina Hui, M.B., B.S., Ph.D., Tibor Csőszi, M.D., Andrea Fülöp, M.D., Maya Gottfried, M.D., Nir Peled, M.D., Ph.D., Ali Tafreshi, M.D., Sinead Cuffe, M.D., Mary O’Brien, M.D., Suman Rao, M.D., Katsuyuki Hotta, M.D., Ph.D., Melanie A. Leiby, Ph.D., Gregory M. Lubiniecki, M.D., Yue Shentu, Ph.D., Reshma Rangwala, M.D., Ph.D., and Julie R. Brahmer, M.D., for the KEYNOTE-024 Investigators*
From Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R.); Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain (D.R.-A.); Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada (A.G.R.); Westmead Hospital and the University of Sydney, Sydney (R.H.), and Southern Medical Day Care Centre, Wollongong, NSW (A.T.) — both in Australia; Jász-Nagykun-Szolnok County Hospital, Szolnok (T.C.), and Országos Korányi TBC és Pulmonológiai Intézet, Budapest (A.F.) — both in Hungary; Meir Medical Center, Kfar-Saba (M.G.), and Davidoff Cancer Center, Tel Aviv University, Petah Tikva (N.P.) — both in Israel; St. James’s Hospital and Cancer Trials Ireland, Dublin (S.C.); the Royal Marsden Hospital, Sutton, Surrey, United Kingdom (M.O.); MedStar Franklin Square Hospital (S.R.) and Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (J.R.B.) — both in Baltimore; Okayama University Hospital, Okayama, Japan (K.H.); and Merck, Kenilworth, NJ (M.A.L., G.M.L., Y.S., R.R.). Address reprint requests to Dr. Brahmer at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting-Blaustein Cancer Research Bldg., 1650 Orleans St., Rm. G94, Baltimore, MD 21287. *A complete list of investigators in the KEYNOTE-024 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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