Systematic Review of Immune Checkpoint Inhibition in Urological Cancers

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%, p = 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 expression 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. As second-line treatment, immune checkpoint inhibitors have changed the perspectives of patients with advanced urothelial and renal cell cancer. Ongoing studies, also assessing novel combination strategies, may further enhance efficacy in earlier treatment lines and disease stages of urological cancers.

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