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

[1] EGFR TKI combination with immunotherapy in non-small cell lung cancer [J].

Ahn, Myung-Ju ;

Sun, Jong-Mu ;

Lee, Se-Hoon ;

Ahn, Jin Seok ;

Park, Keunchil .

EXPERT OPINION ON DRUG SAFETY, 2017, 16 (04) :465-469

[2] Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors [J].

Akbay, Esra A. ;

Koyama, Shohei ;

Carretero, Julian ;

Altabef, Abigail ;

Tchaicha, Jeremy H. ;

Christensen, Camilla L. ;

Mikse, Oliver R. ;

Cherniack, Andrew D. ;

Beauchamp, Ellen M. ;

Pugh, Trevor J. ;

Wilkerson, Matthew D. ;

Fecci, Peter E. ;

Butaney, Mohit ;

Reibel, Jacob B. ;

Soucheray, Margaret ;

Cohoon, Travis J. ;

Janne, Pasi A. ;

Meyerson, Matthew ;

Hayes, D. Neil ;

Shapiro, Geoffrey I. ;

Shimamura, Takeshi ;

Sholl, Lynette M. ;

Rodig, Scott J. ;

Freeman, Gordon J. ;

Hammerman, Peter S. ;

Dranoff, Glenn ;

Wong, Kwok-Kin .

CANCER DISCOVERY, 2013, 3 (12) :1355-1363

[3]

[Anonymous], J CLIN ONCOL S

[4] Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer [J].

Antonia, S. J. ;

Villegas, A. ;

Daniel, D. ;

Vicente, D. ;

Murakami, S. ;

Hui, R. ;

Yokoi, T. ;

Chiappori, A. ;

Lee, K. H. ;

de Wit, M. ;

Cho, B. C. ;

Bourhaba, M. ;

Quantin, X. ;

Tokito, T. ;

Mekhail, T. ;

Planchard, D. ;

Kim, Y. -C. ;

Karapetis, C. S. ;

Hiret, S. ;

Ostoros, G. ;

Kubota, K. ;

Gray, J. E. ;

Paz-Ares, L. ;

de Castro Carpeno, J. ;

Wadsworth, C. ;

Melillo, G. ;

Jiang, H. ;

Huang, Y. ;

Dennis, P. A. ;

Ozguroglu, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (20) :1919-1929

[5] Safety and antitumour activity of durvalumab plus tremelimumab in non-small-cell lung cancer: a multicentre, phase 1b study [J].

Antonia, Scott ;

Goldberg, Sarah B. ;

Balmanoukian, Ani ;

Chaft, Jamie E. ;

Sanborn, Rachel E. ;

Gupta, Ashok ;

Narwal, Rajesh ;

Steele, Keith ;

Gu, Yu ;

Karakunnel, Joyson J. ;

Rizvi, Naiyer A. .

LANCET ONCOLOGY, 2016, 17 (03) :299-308

[6] Safety and clinical activity of durvalumab (MEDI4736), an anti-PD-L1 antibody, in treatment-naive patients with advanced non small-cell lung cancer. [J].

Antonia, Scott Joseph ;

Kim, Sang-We ;

Spira, Alexander I. ;

Ahn, Myung-Ju ;

Ou, Sai-Hong Ignatius ;

Stjepanovic, Neda ;

Fasolo, Angela ;

Jagert, Dirk ;

Ottt, Patrick Alexander ;

Wainberg, Zev A. ;

Wakelee, Heather A. ;

Goldman, Jonathan Wade ;

Kurland, John ;

Rebelatto, Marlon C. ;

Yao, Wenliang ;

Gupta, Ashok Kumar ;

Blake-Haskins, John A. ;

Segal, Neil Howard .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (15)

[7] A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now [J].

Bellmunt, Joaquin ;

Powles, Thomas ;

Vogelzang, Nicholas J. .

CANCER TREATMENT REVIEWS, 2017, 54 :58-67

[8] Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, DUR) plus tremelimumab (TRE) in patients with advanced solid tumors. [J].

Callahan, Margaret K. ;

Odunsi, Kunle ;

Sznol, Mario ;

Nemunaitis, John J. ;

Ott, Patrick Alexander ;

Dillon, Patrick Michael ;

Park, Andrew J. ;

Schwarzenberger, Paul ;

Ricciardi, Toni ;

Macri, Mary J. ;

Ryan, Aileen ;

Venhaus, Ralph Rudolph ;

Wolchok, Jedd D. .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35

[9] Toxicity profiles of immunotherapy [J].

Cousin, S. ;

Seneschal, J. ;

Italiano, A. .

PHARMACOLOGY & THERAPEUTICS, 2018, 181 :91-100

[10] Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation [J].

Freeman, GJ ;

Long, AJ ;

Iwai, Y ;

Bourque, K ;

Chernova, T ;

Nishimura, H ;

Fitz, LJ ;

Malenkovich, N ;

Okazaki, T ;

Byrne, MC ;

Horton, HF ;

Fouser, L ;

Carter, L ;

Ling, V ;

Bowman, MR ;

Carreno, BM ;

Collins, M ;

Wood, CR ;

Honjo, T .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1027-1034

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