TY - JOUR
T1 - Efficacy and tolerability of tremelimumab in locally advanced or metastatic urothelial carcinoma patients who have failed first-line platinum-based chemotherapy
AU - Sharma, Padmanee
AU - Sohn, Joohyuk
AU - Shin, Sang Joon
AU - Oh, Do Youn
AU - Keam, Bhumsuk
AU - Lee, Hyo Jin
AU - Gizzi, Marco
AU - Kalinka, Ewa
AU - de Vos, Filip Y.F.L.
AU - Ruscica, Dario
AU - Ferro, Salvatore
AU - Xiao, Feng
AU - Baverel, Paul
AU - Chen, Cecil Chi Keung
AU - Asubonteng, Kobby
AU - Morsli, Nassim
AU - Dirix, Luc
N1 - Publisher Copyright:
©2019 American Association for Cancer Research.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose: Patients with advanced urothelial carcinoma who fail platinum-containing chemotherapy (treatment fails) have a poor prognosis and limited treatment options. Recent approvals of immune-checkpoint inhibitors confirmed the value of immunomodulatory therapy in urothelial carcinoma. Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4 with demonstrated durable response rate in metastatic melanoma. This is the first study to report the efficacy and safety of tremelimumab in urothelial carcinoma. Patients and Methods: We report the results of the urothelial carcinoma cohort from a phase II, open-label, multicenter study of patients with advanced solid tumors (NCT02527434).two additional cycles) for up to 12 months or until disease progression, initiation of other anticancer therapy, unacceptable toxicity, or consent withdrawal. Results: In 32 evaluable patients with metastatic urothelial carcinoma, objective response rate was 18.8% (95% confidence interval, 7.2–36.4), including complete response (CR) in 2 (6.3%), and partial response in 4 patients (12.5%). Median duration of response has not been reached. Stable disease of ≥12 months was reported in 1 patient (3.1%), yielding a disease control rate at 12 months of 21.9%. Overall, tremelimumab was generally well tolerated; safety results were consistent with the known safety profile. Conclusions: Tremelimumab monotherapy demonstrated clinical activity and durable responses in patients with metastatic urothelial carcinoma. This study is the first in which CR has been observed with tremelimumab as a single agent in urothelial carcinoma.
AB - Purpose: Patients with advanced urothelial carcinoma who fail platinum-containing chemotherapy (treatment fails) have a poor prognosis and limited treatment options. Recent approvals of immune-checkpoint inhibitors confirmed the value of immunomodulatory therapy in urothelial carcinoma. Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4 with demonstrated durable response rate in metastatic melanoma. This is the first study to report the efficacy and safety of tremelimumab in urothelial carcinoma. Patients and Methods: We report the results of the urothelial carcinoma cohort from a phase II, open-label, multicenter study of patients with advanced solid tumors (NCT02527434).two additional cycles) for up to 12 months or until disease progression, initiation of other anticancer therapy, unacceptable toxicity, or consent withdrawal. Results: In 32 evaluable patients with metastatic urothelial carcinoma, objective response rate was 18.8% (95% confidence interval, 7.2–36.4), including complete response (CR) in 2 (6.3%), and partial response in 4 patients (12.5%). Median duration of response has not been reached. Stable disease of ≥12 months was reported in 1 patient (3.1%), yielding a disease control rate at 12 months of 21.9%. Overall, tremelimumab was generally well tolerated; safety results were consistent with the known safety profile. Conclusions: Tremelimumab monotherapy demonstrated clinical activity and durable responses in patients with metastatic urothelial carcinoma. This study is the first in which CR has been observed with tremelimumab as a single agent in urothelial carcinoma.
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U2 - 10.1158/1078-0432.CCR-19-1635
DO - 10.1158/1078-0432.CCR-19-1635
M3 - Article
C2 - 31801732
AN - SCOPUS:85077478172
SN - 1078-0432
VL - 26
SP - 61
EP - 70
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -