Context

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.

Objective

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.

Evidence acquisition

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.

Evidence synthesis

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 18 mo of follow-up were 7.8 mo (95% CI 7.6, 8.1) and 10 mo (95% CI 9.7, 10.5), respectively. A network meta-analysis of two randomized trials revealed no significant difference in the RMST up to 18 mo with PD-1 versus PD-L1 blockade (1.0 mo; 95% CI −0.5, 2.3 mo). Using reconstructed survival data from all six trials, the RMSTs with PD-1 versus PD-L1 blockade up to 12 and 18 mo follow-up were 7.8 mo (95% CI 7.7, 8.2) versus 7.8 mo (95% CI 7.5, 8.2) and 10.1 mo (95% CI 9.6, 10.7) versus 10 mo (95% CI 9.5, 10.6), respectively.

Conclusions

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.

Patient summary

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.

中文翻译：

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铂类耐药转移性尿路上皮癌患者的程序性死亡 1 或程序性死亡配体 1 阻断：系统评价和荟萃分析。

语境

几种抗程序性死亡-1 (anti-PD-1) 和抗程序性死亡配体-1 (anti-PD-L1) 抗体已被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。

客观的

确定接受 PD-1/PD-L1 抑制剂治疗的铂类耐药 mUC 患者的限制平均生存时间 (RMST)，并比较接受 PD-1 与 PD-L1 抑制剂治疗的患者的 RMST。

取证

我们搜索了评估铂类耐药 mUC 患者 PD-1 或​​ PD-L1 抑制的 1、2 和 3 期临床试验。文献回顾和研究选择、数据提取和偏倚风险评估由两名评审员进行。使用一种算法重建生存数据，该算法从已发布的 Kaplan-Meier 曲线中导出单个事件时间数据。计算了具有 95% 置信区间 (CI) 的 RMST。

证据综合

从 836 篇参考文献中，纳入了 6 项临床试验。分别为 1315 名和 736 名接受 PD-1/PD-L1 抑制剂和化疗的患者重建了生存数据。PD-1/PD-L1 阻断长达 12 个月和 18 个月的 RMST 分别为 7.8 个月（95% CI 7.6, 8.1）和 10 个月（95% CI 9.7, 10.5）。一项对两项随机试验的网络荟萃分析显示，PD-1 与 PD-L1 阻断的 RMST 长达 18 个月没有显着差异（1.0 个月；95% CI -0.5, 2.3 个月）。使用来自所有六项试验的重建生存数据，PD-1 与 PD-L1 阻断长达 12 个月和 18 个月的 RMST 分别为 7.8 个月（95% CI 7.7、8.2）和 7.8 个月（95% CI 7.5、8.2） ) 和 10.1 个月 (95% CI 9.6, 10.7) 与 10 个月 (95% CI 9.5, 10.6) 分别。

结论

我们的 RMST 估计值可用作将生存结果背景化的基准，并为未来使用 PD-1/PD-L1 抑制剂的试验设计提供信息。在 mUC 患者中，PD-1 与 PD-L1 阻断产生相当的生存结果。

患者总结

在这项研究中，我们发现接受程序性死亡 1 和程序性死亡配体 1 抑制剂治疗的转移性膀胱癌患者（之前接受过铂类化疗）的结果相似。