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帕博利珠单抗治疗早期三阴性乳腺癌
Pembrolizumab for Early Triple-Negative Breast Cancer


Peter Schmid ... 肿瘤 • 2020.02.27
相关阅读
• sacituzumab govitecan-hziy治疗难治性转移性三阴性乳腺癌 • 三阴性乳腺癌的一个可能的靶点 • 贝伐珠单抗治疗BRCA1/2 突变型三阴性乳腺癌

摘要


背景

既往试验表明,将帕博利珠单抗用于早期三阴性乳腺癌患者后具有良好的抗肿瘤活性和可接受的安全性。目前尚未明确在新辅助化疗的基础上加用帕博利珠单抗可否显著提高在确定性手术时达到病理学完全缓解(定义为乳腺无浸润性癌且淋巴结阴性)的早期三阴性乳腺癌患者百分比。

 

方法

在这项3期试验中,我们将未经治的Ⅱ期或Ⅲ期三阴性乳腺癌患者随机分组(比例为2∶1),分别以下列方案接受了新辅助治疗:一组接受帕博利珠单抗(剂量200 mg,每3周用药1次,用药4个周期)+紫杉醇+卡铂(784例患者;帕博利珠单抗-化疗组),另一组接受安慰剂(每3周用药1次)+紫杉醇+卡铂(390例患者;安慰剂-化疗组);之后两组再接受4个周期的帕博利珠单抗或安慰剂治疗,并且两组均接受多柔比星-环磷酰胺或表柔比星-环磷酰胺治疗。

确定性手术后,患者接受了每3周用药1次的帕博利珠单抗或安慰剂辅助治疗,最多用药9个周期。主要终点是意向治疗人群在确定性手术时的病理学完全缓解以及无事件生存期。

 

结果

在第一次期中分析中,在接受随机分组的前602例患者中,帕博利珠单抗-化疗组和安慰剂-化疗组达到病理学完全缓解的患者百分比分别为64.8%(95%置信区间[CI],59.9~69.5)和51.2%(95% CI,44.1~58.3)(估计的组间差异,13.6个百分点;95% CI,5.4~21.8;P<0.001)。经过中位15.5个月(范围,2.7~25.0)随访后,帕博利珠单抗-化疗组784例患者中的58例(7.4%)和安慰剂-化疗组390例患者中的46例(11.8%)发生了导致其无法接受确定性手术的疾病进展、发生了局部或远处复发或者第二原发肿瘤或已死亡(风险比,0.63;95% CI,0.43~0.93)。在所有治疗阶段,在帕博利珠单抗-化疗组和安慰剂-化疗组中,3级或更高级别治疗相关性不良事件的发生率分别为78.0%和73.0%,分别包括0.4%(3例患者)和0.3%(1例患者)的死亡率。

 

结论

在早期三阴性乳腺癌患者中,帕博利珠单抗+新辅助化疗组中达到病理学完全缓解的患者百分比显著高于安慰剂+新辅助化疗组(由默沙东[默克的子公司]资助;KEYNOTE-522在ClinicalTrials.gov注册号为NCT03036488)。





作者信息

Peter Schmid, M.D., Javier Cortes, M.D., Lajos Pusztai, M.D., Heather McArthur, M.D., Sherko Kümmel, M.D., Jonas Bergh, M.D., Carsten Denkert, M.D., Yeon Hee Park, M.D., Rina Hui, Ph.D., Nadia Harbeck, M.D., Masato Takahashi, M.D., Theodoros Foukakis, M.D., Peter A. Fasching, M.D., Fatima Cardoso, M.D., Michael Untch, M.D., Liyi Jia, Ph.D., Vassiliki Karantza, M.D., Jing Zhao, Ph.D., Gursel Aktan, M.D., Rebecca Dent, M.D., and Joyce O’Shaughnessy, M.D. for the KEYNOTE-522 Investigators*
From Barts Cancer Institute, Queen Mary University of London, London (P.S.); International Oncology Bureau Institute of Oncology, Quirón Group, Madrid, and Vall d’Hebron Institute of Oncology, Barcelona (J.C.) — both in Spain; Yale School of Medicine, Yale Cancer Center, New Haven, CT (L.P.); Cedars-Sinai Medical Center, Los Angeles (H.M.); Kliniken Essen-Mitte, Essen (S.K.), the Institute of Pathology, Philipps-University Marburg and University of Marburg, Marburg (C.D.), the Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Ludwig Maximilian University of Munich, University of Munich, Munich (N.H.), University Hospital Erlangen, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen–European Metropolitan Region of Nuremberg, Erlangen (P.A.F.), and the Breast Cancer Center, Helios Klinikum Berlin-Buch, Berlin (M.U.) — all in Germany; the Department of Oncology-Pathology, Karolinska Institutet and Breast Cancer Center, Theme Cancer, Karolinska University Hospital, Solna, Sweden (J.B., T.F.); Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (Y.H.P.); Westmead Breast Cancer Institute, Westmead Hospital and the University of Sydney, Sydney (R.H.); Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan (M.T.); the Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal (F.C.); Merck, Kenilworth, NJ (L.J., V.K., J.Z., G.A.); the National Cancer Center Singapore, Duke–National University of Singapore Medical School, Singapore (R.D.); and Baylor University Medical Center, Texas Oncology and US Oncology, Dallas (J.O.). Address reprint requests to Dr. Schmid at the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, Old Anatomy Bldg., Charterhouse Sq., London EC1M 6BQ, United Kingdom, or at p.schmid@qmul.ac.uk. *A complete list of investigators who participated in the KEYNOTE-522 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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