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Pembrolizumab治疗非小细胞肺癌的研究
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer


Edward B. Garon ... 肿瘤 呼吸系统疾病 • 2015.05.21
相关阅读
• 新辅助PD-1阻断治疗在可切除肺癌中的应用 • 晚期非小细胞肺癌放化疗后的巩固性免疫疗法 • 晚期非小细胞肺癌的精确诊断和治疗 • 纳武单抗一线治疗Ⅳ期或复发性非小细胞肺癌

训练和验证

 

Tony S K Mok

香港中文大学临床肿瘤学系, 华南肿瘤学重点实验室

 

随着纳武单抗、派姆单抗和阿特朱单抗被批准用于多种恶性肿瘤,包括黑色素瘤、肺癌、霍奇金淋巴瘤和膀胱癌,我们现在已经正式进入了肿瘤免疫学时代。尽管医生和患者都在为这些进展而兴奋不已,但肿瘤免疫学领域仍有很多问题还没有答案。最近Garon等在《新英格兰医学杂志》发表的文章有助于诠释其中一个比较重要的关于派姆单抗用于进展期非小细胞肺癌(NSCLC)的二线治疗的患者选择问题1

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摘要


背景

我们对pembrolizumab抑制细胞程序性死亡受体1(PD-1)在晚期非小细胞肺癌患者中疗效与安全性的进行一期临床试验。我们也试图定义和证实与可能的临床获益相关的PD-1配体(PD-L1)的表达水平。


方法

我们将495例接受pembrolizumab治疗(给药剂量为:2 mg/kg或10 mg/kg,每3周一次;或者10 mg/kg,每2周一次)的患者分为训练组(182例)和验证组(313例)。我们用免疫组织化学法检测肿瘤样本PD-L1的表达水平;在报告结果时,我们报告肿瘤细胞中PD-L1膜染色阳性细胞的百分比(比例评分)。我们的研究中心对治疗效果进行每9周一次的评估。


结果

pembrolizumab常见副作用为疲乏感、瘙痒和食欲减退;不同给药剂量和给药方案之间没有明显的差别。在所有的患者中,客观有效率为19.4%,中位缓解时间为12.5个月;中位无进展生存期为3.7个月,中位总生存期为12个月。在训练组中,我们选择至少50%的肿瘤细胞表达PD-L1作为临界值。在验证组中,对于比例评分至少为50%的患者,有效率为45.2%。对于所有比例评分至少为50%的患者,中位无进展生存期为6.3个月,中位总生存期尚未达到。


结论

pembrolizumab常见副作用易于接受,对晚期非小细胞肺癌患者具有抗肿瘤活性。至少50%的肿瘤细胞表达PD-L1与pembrolizumab疗效改善相关(由默克公司赞助;KEYNOTE-001 ClinicalTrials.gov 注册号,NCT01295827)。





作者信息

Edward B. Garon, M.D., Naiyer A. Rizvi, M.D., Rina Hui, M.B., B.S., Natasha Leighl, M.D., Ani S. Balmanoukian, M.D., Joseph Paul Eder, M.D., Amita Patnaik, M.D., Charu Aggarwal, M.D., Matthew Gubens, M.D., Leora Horn, M.D., Enric Carcereny, M.D., Myung-Ju Ahn, M.D., Enriqueta Felip, M.D., Jong-Seok Lee, M.D., Matthew D. Hellmann, M.D., Omid Hamid, M.D., Jonathan W. Goldman, M.D., Jean-Charles Soria, M.D., Marisa Dolled-Filhart, Ph.D., Ruth Z. Rutledge, M.B.A., Jin Zhang, Ph.D., Jared K. Lunceford, Ph.D., Reshma Rangwala, M.D., Gregory M. Lubiniecki, M.D., Charlotte Roach, B.S., Kenneth Emancipator, M.D., and Leena Gandhi, M.D., for the KEYNOTE-001 Investigators*
The authors' affiliations are listed in the Appendix. Address reprint requests to Dr. Garon at the Translational Oncology Research Laboratory, David Geffen School of Medicine at UCLA, 2825 Santa Monica Blvd., Suite 200, Santa Monica, CA 90404, or ategaron@mednet.ucla.edu. *A complete list of investigators who enrolled patients in the KEYNOTE-001 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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