Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma

被引:16
作者
Hersey, Peter [1 ]
Gowrishankar, Kavitha [1 ]
机构
[1] Univ Sydney, Royal N Shore Hosp, Kolling Med Res Inst, St Leonards, NSW 2065, Australia
关键词
1-year survival; melanoma; PD-L1; PD1 checkpoint inhibitors; PFS; response rates; METASTATIC MELANOMA; BRAF INHIBITION; EXPRESSION; SAFETY; THERAPY; CELLS; NRAS; CHEMOTHERAPY; COMBINATION; DACARBAZINE;
D O I
10.2217/fon.14.205
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pembrolizumab (MK-3475) is a monoclonal antibody that binds to the PD-1 receptor on T cells and prevents binding to its ligands PD-L1 and PD-L2. Blocking this receptor frees T cells from the inhibitory effects of PD-L1 and allows them to mediate antitumor effects against cancer cells. In a large Phase I study of 411 patients with melanoma, high durable response rates over a range of doses and schedules have been shown with very little toxicity. A Phase III study of pembrolizumab comparing two schedules of administration with the current standard treatment with the anti-CTLA-4 monoclonal antibody is in progress. Combinations with other checkpoint inhibitors as well as other anticancer agents are also being evaluated. Approval of pembrolizumab for the treatment of melanoma is expected.
引用
收藏
页码:133 / 140
页数:8
相关论文
共 51 条
[1]  
[Anonymous], 2014 AM SOC CLIN ONC
[2]  
[Anonymous], 2013, ASCO M S
[3]   The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment [J].
Ascierto, Paolo A. ;
Capone, Mariaelena ;
Urba, Walter J. ;
Bifulco, Carlo B. ;
Botti, Gerardo ;
Lugli, Alessandro ;
Marincola, Francesco M. ;
Ciliberto, Gennaro ;
Galon, Jerome ;
Fox, Bernard A. .
JOURNAL OF TRANSLATIONAL MEDICINE, 2013, 11
[4]   Biomarkers for Immunostimulatory Monoclonal Antibodies in Combination Strategies for Melanoma and Other Tumor Types [J].
Ascierto, Paolo A. ;
Kalos, Michael ;
Schaer, David A. ;
Callahan, Margaret K. ;
Wolchok, Jedd D. .
CLINICAL CANCER RESEARCH, 2013, 19 (05) :1009-1020
[5]   Final Version of 2009 AJCC Melanoma Staging and Classification [J].
Balch, Charles M. ;
Gershenwald, Jeffrey E. ;
Soong, Seng-jaw ;
Thompson, John F. ;
Atkins, Michael B. ;
Byrd, David R. ;
Buzaid, Antonio C. ;
Cochran, Alistair J. ;
Coit, Daniel G. ;
Ding, Shouluan ;
Eggermont, Alexander M. ;
Flaherty, Keith T. ;
Gimotty, Phyllis A. ;
Kirkwood, John M. ;
McMasters, Kelly M. ;
Mihm, Martin C., Jr. ;
Morton, Donald L. ;
Ross, Merrick I. ;
Sober, Arthur J. ;
Sondak, Vernon K. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (36) :6199-6206
[6]   BET Protein Function Is Required for Inflammation: Brd2 Genetic Disruption and BET Inhibitor JQ1 Impair Mouse Macrophage Inflammatory Responses [J].
Belkina, Anna C. ;
Nikolajczyk, Barbara S. ;
Denis, Gerald V. .
JOURNAL OF IMMUNOLOGY, 2013, 190 (07) :3670-3678
[7]   Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function [J].
Boni, Andrea ;
Cogdill, Alexandria P. ;
Dang, Ping ;
Udayakumar, Durga ;
Njauw, Ching-Ni Jenny ;
Sloss, Callum M. ;
Ferrone, Cristina R. ;
Flaherty, Keith T. ;
Lawrence, Donald P. ;
Fisher, David E. ;
Tsao, Hensin ;
Wargo, Jennifer A. .
CANCER RESEARCH, 2010, 70 (13) :5213-5219
[8]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[9]   Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy [J].
Buckanovich, Ronald J. ;
Facciabene, Andrea ;
Kim, Sarah ;
Benencia, Fabian ;
Sasaroli, Dimitra ;
Balint, Klara ;
Katsaros, Dionysios ;
O'Brien-Jenkins, Anne ;
Gimotty, Phyllis A. ;
Coukos, George .
NATURE MEDICINE, 2008, 14 (01) :28-36
[10]  
BURKE PJ, 1971, CANCER, V27, P744, DOI 10.1002/1097-0142(197103)27:3<744::AID-CNCR2820270335>3.0.CO