TY - JOUR
T1 - Profile of pembrolizumab in the treatment of patients with unresectable or metastatic urothelial carcinoma
AU - Inokuchi, Junichi
AU - Eto, Masatoshi
N1 - Funding Information:
This study was supported in part by JSPS KAKENHI Grant Number JP16K11010. The authors would like to thank H. Nikki March, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Publisher Copyright:
© 2019 Inokuchi and Eto.
PY - 2019
Y1 - 2019
N2 - The prognosis of patients with unresectable or metastatic urothelial carcinoma (UC) is poor. Platinum-based chemotherapy has been the standard first-line treatment in these patients for the past decade; however, the 5-year overall survival (OS) rate is only 13-22%. Recent advances in cancer immunology research have highlighted the pivotal role of the immune system in cancer development and progression, and new immune checkpoint inhibitors (ICIs) have demonstrated efficacy in a large variety of tumors including UC. Currently, five ICIs, including two anti-PD-1 antibodies (pembrolizumab and nivolumab) and three anti-PD-L1 antibodies (atezolizumab, avelumab, and durvalumab), have been granted approval by the US Food and Drug Administration (FDA) for patients with unresectable or metastatic UC who recurred or progressed after platinum-based chemotherapy. Among these agents, only pembrolizumab is supported by strong evidence from a large randomized Phase III trial (KEYNOTE-045). This trial demonstrated statistically significant improvements in OS for patients assigned to the pembrolizumab arm compared with the chemotherapy arm, both in the total population (HR 0.73; P=0.002) and in the population with high PD-L1 expression (HR 0.57; P=0.005). For patients with cisplatin-ineligible UC, pembrolizumab and atezolizumab were approved based on Phase II studies, with limitations on the use of these agents in patients with high tumor PD-L1 expression later imposed by the FDA. In conclusion, pembrolizumab may be a potential first-choice second-line therapy for unresectable or metastatic UC patients following platinum-based chemotherapy. Several Phase III trials are ongoing to evaluate the efficacy and toxicity of combination therapies of ICIs with chemotherapy, and ICIs with other ICIs with or without chemotherapy as firstline therapy. The results of these trials might redirect treatment strategies for patients with unresectable or metastatic UC.
AB - The prognosis of patients with unresectable or metastatic urothelial carcinoma (UC) is poor. Platinum-based chemotherapy has been the standard first-line treatment in these patients for the past decade; however, the 5-year overall survival (OS) rate is only 13-22%. Recent advances in cancer immunology research have highlighted the pivotal role of the immune system in cancer development and progression, and new immune checkpoint inhibitors (ICIs) have demonstrated efficacy in a large variety of tumors including UC. Currently, five ICIs, including two anti-PD-1 antibodies (pembrolizumab and nivolumab) and three anti-PD-L1 antibodies (atezolizumab, avelumab, and durvalumab), have been granted approval by the US Food and Drug Administration (FDA) for patients with unresectable or metastatic UC who recurred or progressed after platinum-based chemotherapy. Among these agents, only pembrolizumab is supported by strong evidence from a large randomized Phase III trial (KEYNOTE-045). This trial demonstrated statistically significant improvements in OS for patients assigned to the pembrolizumab arm compared with the chemotherapy arm, both in the total population (HR 0.73; P=0.002) and in the population with high PD-L1 expression (HR 0.57; P=0.005). For patients with cisplatin-ineligible UC, pembrolizumab and atezolizumab were approved based on Phase II studies, with limitations on the use of these agents in patients with high tumor PD-L1 expression later imposed by the FDA. In conclusion, pembrolizumab may be a potential first-choice second-line therapy for unresectable or metastatic UC patients following platinum-based chemotherapy. Several Phase III trials are ongoing to evaluate the efficacy and toxicity of combination therapies of ICIs with chemotherapy, and ICIs with other ICIs with or without chemotherapy as firstline therapy. The results of these trials might redirect treatment strategies for patients with unresectable or metastatic UC.
UR - http://www.scopus.com/inward/record.url?scp=85070018519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070018519&partnerID=8YFLogxK
U2 - 10.2147/CMAR.S167708
DO - 10.2147/CMAR.S167708
M3 - Article
AN - SCOPUS:85070018519
SN - 1179-1322
VL - 11
SP - 4519
EP - 4528
JO - Cancer Management and Research
JF - Cancer Management and Research
ER -
