Safety and efficacy of durvalumab (MEDI4736) in various solid tumors

被引：35

作者：

Yang, Hui ^{[1
,2
]}

Shen, Kai ^{[3
,4
,5
]}

Zhu, Chenjing ^{[3
,4
,5
]}

Li, Qingfang ^{[3
,4
,5
]}

Zhao, Yunuo ^{[2
]}

Ma, Xuelei ^{[3
,4
,5
]}

机构：

[1] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu, Peoples R China

[2] Sichuan Univ, West China Hosp, West China Sch Med, Chengdu, Sichuan, Peoples R China

[3] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China

[4] Sichuan Univ, West China Hosp, Canc Ctr, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China

[5] Collaborat Innovat Ctr, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China

来源：

DRUG DESIGN DEVELOPMENT AND THERAPY | 2018年 / 12卷

关键词：

durvalumab; solid cancers; adverse effects; efficacy; meta-analysis; CELL LUNG-CANCER; ACQUIRED-RESISTANCE; NEGATIVE REGULATION; PD-L1; EXPRESSION; PHASE-I; BLOCKADE; IMMUNOTHERAPY; RECEPTOR; COMBINATION; TOXICITIES;

D O I：

10.2147/DDDT.S162214

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Introduction: The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors. Methods: A systematic search of PubMed, Embase, and related articles was performed. Safety data were analyzed using Comprehensive Meta-Analysis software program version 2. Ultimately. 17 studies with 1,529 patients were included in our analysis. Results: The major adverse events associated with durvalumab were pruritus and fatigue, while pruritus, increased alanine transaminase, and increased aspartate aminotransferase were common among patients treated with a combination of durvalumab and tremelimumab. Higher PD-L1 expression was associated with a superior objective response rate. Conclusion: Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved prognosis. PD-L1 expression is a biomarker of the efficacy of durvalumab.

引用

页码：2085 / 2096

页数：12

共 52 条

[41] Durvalumab: First Global Approval [J].

Syed, Yahiya Y. .

DRUGS, 2017, 77 (12) :1369-1376

[42] A phase 1 study to assess the safety and tolerability of tremelimumab alone and in combination with MEDI4736 in Japanese patients with advanced solid malignancies [J].

Takahashi, Y. ;

Fujikawa, K. ;

Sagawa, T. ;

Fujiwara, Y. ;

Iwasa, S. ;

Yamamoto, N. ;

Sugeno, M. ;

Tsuno, H. .

EUROPEAN JOURNAL OF CANCER, 2015, 51 :S107-S107

[43] Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer [J].

Topalian, Suzanne L. ;

Hodi, F. Stephen ;

Brahmer, Julie R. ;

Gettinger, Scott N. ;

Smith, David C. ;

McDermott, David F. ;

Powderly, John D. ;

Carvajal, Richard D. ;

Sosman, Jeffrey A. ;

Atkins, Michael B. ;

Leming, Philip D. ;

Spigel, David R. ;

Antonia, Scott J. ;

Horn, Leora ;

Drake, Charles G. ;

Pardoll, Drew M. ;

Chen, Lieping ;

Sharfman, William H. ;

Anders, Robert A. ;

Taube, Janis M. ;

McMiller, Tracee L. ;

Xu, Haiying ;

Korman, Alan J. ;

Jure-Kunkel, Maria ;

Agrawal, Shruti ;

McDonald, Daniel ;

Kollia, Georgia D. ;

Gupta, Ashok ;

Wigginton, Jon M. ;

Sznol, Mario .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2443-2454

[44] Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer [J].

Twyman-Saint Victor, Christina ;

Rech, Andrew J. ;

Maity, Amit ;

Rengan, Ramesh ;

Pauken, Kristen E. ;

Stelekati, Erietta ;

Benci, Joseph L. ;

Xu, Bihui ;

Dada, Hannah ;

Odorizzi, Pamela M. ;

Herati, Ramin S. ;

Mansfield, Kathleen D. ;

Patsch, Dana ;

Amaravadi, Ravi K. ;

Schuchter, Lynn M. ;

Ishwaran, Hemant ;

Mick, Rosemarie ;

Pryma, Daniel A. ;

Xu, Xiaowei ;

Feldman, Michael D. ;

Gangadhar, Tara C. ;

Hahn, Stephen M. ;

Wherry, E. John ;

Vonderheide, Robert H. ;

Minn, Andy J. .

NATURE, 2015, 520 (7547) :373-+

[45] Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC). [J].

Wainberg, Zev A. ;

Segal, Neil Howard ;

Jaeger, Dirk ;

Lee, Kyung-Hun ;

Marshall, John ;

Antonia, Scott Joseph ;

Butler, Marcus ;

Sanborn, Rachel E. ;

Nemunaitis, John J. ;

Carlson, Cheryl Ann ;

Finn, Richard S. ;

Jin, Xiaoping ;

Antal, Joyce ;

Gupta, Ashok Kumar ;

Massard, Christophe .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35

[46] Primary and acquired resistance to PD-1/PD-L1 blockade in cancer treatment [J].

Wang, Qiaohong ;

Wu, Xia .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2017, 46 :210-219

[47] Toxicities of Immunotherapy for the Practitioner [J].

Weber, Jeffrey S. ;

Yang, James C. ;

Atkins, Michael B. ;

Disis, Mary L. .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (18) :2092-U154

[48]

WEBER JS, 2015, J CLIN ONCOL S, V33

[49] The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation [J].

Wolchok, Jedd D. ;

Saenger, Yvonne .

ONCOLOGIST, 2008, 13 :2-9

[50] Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1 [J].

Zak, Krzysztof M. ;

Kitel, Radoslaw ;

Przetocka, Sara ;

Golik, Przemyslaw ;

Guzik, Katarzyna ;

Musielak, Bogdan ;

Domling, Alexander ;

Dubin, Grzegorz ;

Holak, Tad A. .

STRUCTURE, 2015, 23 (12) :2341-2348

← 1 2 3 4 5 6 →