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Immune checkpoint inhibitors in urothelial cancer: recent updates and future outlook

Authors Gopalakrishnan D, Koshkin VS, Ornstein MC, Papatsoris A, Grivas P

Received 3 December 2017

Accepted for publication 14 March 2018

Published 5 June 2018 Volume 2018:14 Pages 1019—1040


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Garry Walsh

Dharmesh Gopalakrishnan,1 Vadim S Koshkin,2 Moshe C Ornstein,2 Athanasios Papatsoris,3 Petros Grivas2,4

1Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA; 2Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA; 3Sismanoglio General Hospital, University of Athens School of Medicine, Athens, Greece; 4Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA

Abstract: Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration. A plethora of clinical trials are ongoing in diverse disease settings, employing agents targeting PD-1/PD-L1 and related immune checkpoint pathways. While reactivating anti-tumor immunity, these agents may lead to a unique constellation of immune-related adverse events, which may warrant discontinuation of therapy and potential use of immunosuppression. Novel combinations with various treatment modalities and optimal sequencing of active therapies are being investigated in prospective clinical trials and retrospective registries. At the era of precision molecular medicine, and since patients do not respond uniformly to these agents, there is a growing need for identification and validation of biomarkers that can accurately predict treatment response and assist in patient selection. This review discusses current updates and future directions of immunotherapy in advanced UC.

Keywords: immunotherapy, urothelial carcinoma, bladder cancer, PD-1, PD-L1, CTLA-4, biomarkers, immune-related adverse events

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