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  • Programmed Death-1 or Progr...
    Niglio, Scot A.; Jia, Rachel; Ji, Jiayi; Ruder, Samuel; Patel, Vaibhav G.; Martini, Alberto; Sfakianos, John P.; Marqueen, Kathryn E.; Waingankar, Nikhil; Mehrazin, Reza; Wiklund, Peter; Oh, William K.; Mazumdar, Madhu; Ferket, Bart S.; Galsky, Matthew D.

    European urology, 12/2019, Letnik: 76, Številka: 6
    Journal Article

    Several anti-programmed death-1 (anti-PD-1) and anti-programmed death ligand-1 (anti-PD-L1) antibodies have been approved by regulatory authorities for treatment of platinum-resistant metastatic urothelial cancer (mUC). The impact of these therapies on survival, and comparability of PD-1 versus PD-L1 blockade are unknown. To determine the restricted mean survival time (RMST) of patients with platinum-resistant mUC treated with PD-1/PD-L1 inhibitors and to compare RMSTs in patients treated with PD-1 versus PD-L1 inhibitors. We searched for phase 1, 2, and 3 clinical trials that assessed PD-1 or PD-L1 inhibition for patients with platinum-resistant mUC. Literature review and study selection, data abstraction, and risk of bias assessment were performed by two reviewers. Survival data were reconstructed using an algorithm that derives individual time-to-event data from published Kaplan-Meier curves. The RMST with 95% confidence interval (CIs) was calculated. From 836 references, six clinical trials were included. Survival data were reconstructed for 1315 and 736 patients treated with PD-1/PD-L1 inhibitors and chemotherapy, respectively. The RMSTs with PD-1/PD-L1 blockade up to 12 and 18mo of follow-up were 7.8mo (95% CI 7.6, 8.1) and 10mo (95% CI 9.7, 10.5), respectively. A network meta-analysis of two randomized trials revealed no significant difference in the RMST up to 18mo with PD-1 versus PD-L1 blockade (1.0mo; 95% CI −0.5, 2.3mo). Using reconstructed survival data from all six trials, the RMSTs with PD-1 versus PD-L1 blockade up to 12 and 18mo follow-up were 7.8mo (95% CI 7.7, 8.2) versus 7.8mo (95% CI 7.5, 8.2) and 10.1mo (95% CI 9.6, 10.7) versus 10mo (95% CI 9.5, 10.6), respectively. Our RMST estimates may be used as benchmarks to contextualize survival outcomes and inform future trial design with PD-1/PD-L1 inhibitors. PD-1 versus PD-L1 blockade in patients with mUC yields comparable survival outcomes. In this study, we found that outcomes for patients with metastatic bladder cancer treated with programmed death-1 and programmed death ligand-1 inhibitors, who received prior platinum-based chemotherapy, were similar. Restricted mean survival time estimates may be used to benchmark survival outcomes and inform future trial design.Programmed death-1 and programmed death ligand-1 blockade in patients with platinum-resistant metastatic urothelial cancer yield comparable survival outcomes.