Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Institute for Health Care Delivery Science, Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eur Urol. 2019 Dec;76(6):782-789. doi: 10.1016/j.eururo.2019.05.037. Epub 2019 Jun 11.
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.
已有几种抗程序性死亡-1（抗 PD-1）和抗程序性死亡配体-1（抗 PD-L1）抗体获得监管机构批准，用于治疗铂类耐药的转移性尿路上皮癌（mUC）。这些疗法对生存的影响以及 PD-1 与 PD-L1 阻断的可比性尚不清楚。
确定接受 PD-1/PD-L1 抑制剂治疗的铂类耐药 mUC 患者的受限平均生存时间（RMST），并比较接受 PD-1 与 PD-L1 抑制剂治疗的患者的 RMST。
我们搜索了评估 PD-1 或 PD-L1 抑制作用治疗铂类耐药 mUC 患者的 1 期、2 期和 3 期临床试验。由两名审查员进行文献回顾和研究选择、数据提取和偏倚风险评估。使用从已发表的 Kaplan-Meier 曲线中得出个体时间事件数据的算法来重建生存数据。计算 RMST 和 95%置信区间（CI）。
从 836 篇参考文献中，纳入了 6 项临床试验。分别为接受 PD-1/PD-L1 抑制剂和化疗治疗的 1315 例和 736 例患者重建了生存数据。接受 PD-1/PD-L1 阻断治疗至 12 个月和 18 个月的 RMST 分别为 7.8 个月（95%CI 7.6，8.1）和 10.0 个月（95%CI 9.7，10.5）。两项随机试验的网络荟萃分析显示，至 18 个月时，PD-1 与 PD-L1 阻断的 RMST 无显著差异（1.0 个月；95%CI-0.5，2.3 个月）。使用来自所有 6 项试验的重建生存数据，接受 PD-1 与 PD-L1 阻断治疗至 12 个月和 18 个月的 RMST 分别为 7.8 个月（95%CI 7.7，8.2）与 7.8 个月（95%CI 7.5，8.2）和 10.1 个月（95%CI 9.6，10.7）与 10.0 个月（95%CI 9.5，10.6）。
我们的 RMST 估计值可作为背景参考，以了解生存结果，并为未来的 PD-1/PD-L1 抑制剂试验设计提供信息。mUC 患者中 PD-1 与 PD-L1 阻断的生存结果相似。
在这项研究中，我们发现先前接受过铂类化疗的转移性膀胱癌患者接受程序性死亡-1 和程序性死亡配体-1 抑制剂治疗的结果相似。
