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阿替利珠单抗联合贝伐珠单抗治疗不可切除的肝细胞癌
Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma


Richard S. Finn ... 肿瘤 • 2020.05.14
相关阅读
• 贝伐珠单抗联合阿替利珠单抗治疗晚期肝细胞癌 • 阿替利珠单抗联合贝伐珠单抗——肝癌治疗的里程碑 • 肝细胞癌

摘要


背景

在对不可切除的肝细胞癌患者进行的一项1b期试验中,阿替利珠单抗(atezolizumab)和贝伐珠单抗联合治疗显示了令人鼓舞的抗肿瘤活性和安全性。

 

方法

在一项全球性、开放标签、3期试验中,我们以2∶1的比例将既往未接受过全身性治疗的不可切除的肝细胞癌患者随机分组,分别接受阿替利珠单抗+贝伐珠单抗治疗或索拉非尼治疗,直至发生无法接受的毒性作用或者临床获益丧失。联合主要终点是意向治疗人群的总生存期和无进展生存期,由独立的审核机构根据《实体瘤疗效评价标准》(Response Evaluation Criteria in Solid Tumors)1.1版(RECIST 1.1)评估。

 

结果

意向治疗人群包括阿替利珠单抗-贝伐珠单抗组336例患者和索拉非尼组165例患者。在主要分析时(2019年8月29日),阿替利珠单抗-贝伐珠单抗组与索拉非尼组相比的死亡的风险比为0.58(95%置信区间[CI],0.42~0.79;P<0.001)。在阿替利珠单抗-贝伐珠单抗组和索拉非尼组中,12个月时的总生存率分别为67.2%(95% CI,61.3~73.1)和54.6%(95% CI,45.2~64.0)。两组的中位无进展生存期分别为6.8个月(95% CI,5.7~8.3)和4.3个月(95% CI,4.0~5.6)(疾病进展或死亡的风险比,0.59;95% CI,0.47~0.76;P<0.001)。在接受了至少1剂阿替利珠单抗-贝伐珠单抗治疗的329例患者和接受了至少1剂索拉非尼治疗的156例患者中,分别有56.5%和55.1%发生了3级或4级不良事件。阿替利珠单抗-贝伐珠单抗组15.2%的患者发生了3级或4级高血压。但其他高级别毒性作用罕见。

 

结论

在不可切除的肝细胞癌患者中,阿替利珠单抗联合贝伐珠单抗使患者达到了优于索拉非尼的总生存期和无进展生存期结局(由罗氏制药/基因泰克资助,在ClinicalTrials.gov注册号为NCT03434379)。





作者信息

Richard S. Finn, M.D., Shukui Qin, M.D., Masafumi Ikeda, M.D., Peter R. Galle, M.D., Michel Ducreux, M.D., Tae-You Kim, M.D., Masatoshi Kudo, M.D., Valeriy Breder, M.D., Philippe Merle, M.D., Ahmed O. Kaseb, M.D., Daneng Li, M.D., Wendy Verret, Ph.D., Derek-Zhen Xu, M.D., Sairy Hernandez, Ph.D., Juan Liu, Ph.D., Chen Huang, M.D., Sohail Mulla, Ph.D., Yulei Wang, Ph.D., Ho Yeong Lim, M.D., Andrew X. Zhu, M.D., Ph.D., and Ann-Lii Cheng, M.D., for the IMbrave150 Investigators*
From the Jonsson Comprehensive Cancer Center, Geffen School of Medicine at UCLA, Los Angeles (R.S.F.), the City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte (D.L.), and Genentech, South San Francisco (W.V., S.H., Y.W.) — all in California; the People’s Liberation Army Cancer Center, Jinling Hospital, Nanjing (S.Q.), and Roche Product Development (D.­Z.X., J.L., C.H.) and Jiahui International Cancer Center, Jiahui Health (A.X.Z.), Shanghai — all in China; National Cancer Center Hospital East, Kashiwa (M.I.), and Kindai University Faculty of Medicine, Osaka (M.K.) — both in Japan; University Medical Center Mainz, Mainz, Germany (P.R.G.); Gustave Roussy Cancer Center, Paris­Saclay University, Villejuif (M.D.), and University Hospital La Croix­Rousse, Lyon (P.M.) — both in France; Seoul National University College of Medicine (T.­Y.K.) and Sam­ sung Medical Center, Sungkyunkwan University School of Medicine (H.Y.L.) — both in Seoul, South Korea; N.N. Blokhin Russian Cancer Research Center, Moscow (V.B.); the University of Texas M.D. Anderson Cancer Center, Houston (A.O.K.); Hoffmann–La Roche, Mississauga, ON, Canada (S.M.); Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston (A.X.Z.); and the National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei (A.­L.C.). Address reprint requests to Dr. Cheng at the National Taiwan University Cancer Center and National Taiwan University Hospital, 7 Chung-Shan South Rd., Taipei, 10002, Taiwan, or at alcheng@ntu.edu.tw; or to Dr. Finn at the Department of Medicine, Division of Hematology/ Oncology, Geffen School of Medicine at UCLA, 2825 Santa Monica Blvd., Suite 200, Santa Monica, CA, 90404, or at rfinn@ mednet.ucla.edu. *A list of the IMbrave150 trial investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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