EURURO Vol. 72 No. 3

Review – Urothelial Cancer

Systematic Review of Immune Checkpoint Inhibition in

Urological Cancers

Maud Rijnders

a ,

Ronald de Wit

a , * ,

Joost L. Boormans

b ,

Martijn P.J. Lolkema

a ,

Astrid A.M. van der Veldt

Department of Medical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands;

Department of Urology, Erasmus MC-Cancer Institute,

Rotterdam, The Netherlands

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 4 1 1 – 4 2 3

ava ilable at

www.sciencedirect.com

journal homepage:

www.eu ropeanurology.com

Article info

Article history:

Accepted June 7, 2017

Associate Editor:

Giacomo Novara

Keywords:

Immune checkpoint inhibitors

Immunotherapy

Programmed cell death 1

Programmed cell death receptor

ligand 1

Cytotoxic T lymphocyte–

associated protein 4

Urothelial cell cancer

Renal cell cancer

Prostate cancer

Urological cancer

Abstract

Context:

In patients with advanced and metastatic urological cancers, clinical outcome

may be improved by immune checkpoint inhibitors (ICIs).

Objective:

To systematically review relevant literature on efficacy and safety of ICIs in

patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer

(RCC), and prostate cancer.

Evidence acquisition:

Relevant databases, including Medline, Embase, and the Cochrane

Library, were searched up to March 16, 2017. A narrative review of randomized clinical

trials (RCTs) was performed.

Evidence synthesis:

Six RCTs were included for the systematic review. In platinum-

pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer

median overall survival (OS; 10.3 vs 7.4 mo), a higher objective response rate (ORR;

21.1% vs 11.4%,

= 0.001), and a lower adverse event rate (60.9% vs 90.2%). Three RCTs

assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 vs

19.6 mo) and the ORR (25% vs 5%) were higher in patients treated with nivolumab

compared with second-line everolimus. In all three studies, the safety profile of

nivolumab was favorable. In patients with metastatic castration-resistant prostate

cancer, two RCTs were identified, which did not show significant benefits for ipilimumab

over placebo. In UCC and RCC, there was no conclusive association between programmed

cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome

during pembrolizumab and nivolumab treatment, respectively.

Conclusion:

In metastatic UCC and RCC, pembrolizumab and nivolumab have superior

efficacy and safety to second-line chemotherapy and everolimus, respectively. No

beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expres-

sion status is currently not suitable as a predictive marker for treatment outcome.

Patient summary:

Immune checkpoint inhibitors are able to reactivate the immune

system against tumor cells. In second-line setting, pembrolizumab and nivolumab are

safe and confer survival benefit in advanced urothelial cell and renal cell cancer,

respectively.

* Corresponding author. Department of Medical Oncology, Erasmus MC - Cancer Institute, Groene

Hilledijk 301, 3075 EA Rotterdam, The Netherlands. Tel. +31 10 7041505; Fax: +31 10 7041003.

E-mail address:

r.dewit@erasmusmc.nl

(R. de Wit).

http://dx.doi.org/10.1016/j.eururo.2017.06.012

0302-2838/