Very few therapeutic options are available in patients with advanced or metastatic urothelial carcinoma progressed or unfit to platinum based therapy. After decades of failures, a new classes of agents: the immune-checkpoint inhibitors seem to be a new promising hope for these patients. However, to date of the two randomized studies comparing these compounds to standard chemotherapy only one trial showed a clear survival advantage in this setting.
We performed a systematic review and meta-analysis to assess the efficacy, in terms of overall survival, of single agent immune-checkpoint inhibitors vs. single agent chemotherapy as second-line treatment. Moreover, we evaluated the assessed ORR of single-agent immune-checkpoint inhibitors in patients with advanced urothelial cancer exploring the predictive value of patients’ selection according to PD-L1 expression. To do this, we reviewed clinical trials published on Pubmed/Medline, Cochrane library and clinical abstracts presented on main International meeting between 2014 and 2018.
Systematic review included randomized (n = 2) and non-randomized (n = 9) clinical trials. We restricted meta-analysis to trials exploring immune-checkpoint inhibitors in previously platinum treated patients.In randomized trials, immune checkpoint inhibitors were associated with a significant improvement of overall survival compared to chemotherapy in unselected patients, with pooled Hazard Ratio 0.80 (95% confidence interval 0.69 – 0.93, p = 0.003), while the difference was not statistically significant in the subgroup of patients selected for the highest PD-L1 expression (Hazard Ratio 0.72, 95% confidence interval 0.48 – 1.09, p = 0.12). Polled probability of objective response was 0.18 (95% confidence interval 0.16 – 0.20) in unselected patients and 0.27% (95% confidence interval 0.25 – 0.32) in patients selected for the highest expression of PD-L1.
Immunotherapy showed a significant survival advantage in patients not selected for PD-L1 expression while both OS and ORR analysis suggested that the predictive value of PD-L1 expression is far from being optimal.
Clinical trial identification
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All authors have declared no conflicts of interest.