TY - JOUR
T1 - The emerging role of immunotherapy in advanced urothelial cancers
AU - Tabayoyong, William
AU - Gao, Jianjun
N1 - Publisher Copyright:
© 2018 Lippincott Williams and Wilkins. All rights reserved.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Purpose of review Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. Recent findings The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity. Aggressive bladder cancer cells express aberrantly high levels of PD-L1, hijacking the normal immune-regulatory pathway to evade detection and destruction by the immune system. Blockade of the PD-1/PD-L1 axis with immune checkpoint inhibitors augments the immune system's ability to eradicate bladder cancer with impressive safety and tolerability profiles. Summary Recent clinical trials demonstrate that patients with metastatic urothelial carcinoma are responsive to immune checkpoint inhibitor therapy. Optimal treatment regimens are still under development, but activity has been demonstrated in both the first and second-line setting for metastatic disease.
AB - Purpose of review Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research. Recent findings The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity. Aggressive bladder cancer cells express aberrantly high levels of PD-L1, hijacking the normal immune-regulatory pathway to evade detection and destruction by the immune system. Blockade of the PD-1/PD-L1 axis with immune checkpoint inhibitors augments the immune system's ability to eradicate bladder cancer with impressive safety and tolerability profiles. Summary Recent clinical trials demonstrate that patients with metastatic urothelial carcinoma are responsive to immune checkpoint inhibitor therapy. Optimal treatment regimens are still under development, but activity has been demonstrated in both the first and second-line setting for metastatic disease.
KW - bladder cancer
KW - immune checkpoint inhibitor
KW - programmed death 1 receptor
KW - programmed death ligand-1
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U2 - 10.1097/CCO.0000000000000445
DO - 10.1097/CCO.0000000000000445
M3 - Review article
C2 - 29553950
AN - SCOPUS:85045520692
SN - 1040-8746
VL - 30
SP - 172
EP - 180
JO - Current opinion in oncology
JF - Current opinion in oncology
IS - 3
ER -