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程序性死亡(PD)-1或PD配体1抑制剂治疗中断后晚期尿路上皮癌患者的结局

Outcomes in patients with advanced urothelial carcinoma after discontinuation of programmed death (PD)-1 or PD ligand 1 inhibitor therapy.

作者信息

Sonpavde Guru, Pond Gregory R, Mullane Stephanie, Ramirez Ana A, Vogelzang Nicholas J, Necchi Andrea, Powles Thomas, Bellmunt Joaquim

机构信息

UAB Comprehensive Cancer Center, Birmingham, AL, USA.

McMaster University, Hamilton, ON, Canada.

出版信息

BJU Int. 2017 Apr;119(4):579-584. doi: 10.1111/bju.13674. Epub 2016 Oct 26.

Abstract

OBJECTIVE

To study the subsequent therapy and disease outcomes of patients with advanced urothelial carcinoma (UC) after discontinuation of programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.

PATIENTS AND METHODS

We performed a retrospective analysis to examine outcomes and systemic therapy administration after PD-1/PD-L1 inhibitor therapy in patients with advanced UC. Data on demographics and therapy administered were collected from the institutions involved in the study. Univariable Cox regression analyses were performed to examine the clinical factors potentially associated with overall survival (OS) after PD-1/PD-L1 inhibitor therapy.

RESULTS

Data from 62 patients were available from four institutions, with capture of subsequent therapy and outcomes after checkpoint inhibitor immunotherapy. The median patient age was 65.5 years and 51 patients (82.3%) were male. The median (range) duration of PD-1/PD-L1 inhibitor therapy in 55 patients for whom these data were available was 64 (7-669) days. Of these, 22 patients (35.5%) received post-PD-1/PD-L1 inhibitor therapy through a variety of different chemotherapy regimens (n = 16), chemobiological combination (n = 1), biological agents (n = 4) and immunotherapy (n = 1). The median (range) time from last PD-1/PD-L1 inhibitor therapy to subsequent therapy was 58 (14-242) days. The median OS of all patients after completion of PD-1/PD-L1 inhibitor therapy was 149 days (95% confidence interval [CI]: 75-359). Among those who received some post-PD-1/PD-L1 inhibitor therapy, the median OS was 182 days (95% CI: 121-372), and the median time to progression was 124 days (95% CI: 61-273) from the start of post-PD-1/PD-L1 therapy. Among these 22 patients, the only significant baseline prognostic factor associated with OS was performance status.

CONCLUSIONS

In this dataset, 35.5% of patients with advanced UC received systemic therapy after salvage therapy with PD-1/PD-L1 inhibitors. Outcomes after subsequent therapy appear similar to those historically observed in patients who had not received prior PD-1/PD-L1 inhibitor therapy. Further study of patients receiving post-PD-1/PD-L1 inhibitor therapy is warranted to identify factors associated with outcomes and potentially synergistic sequences.

摘要

目的

研究晚期尿路上皮癌(UC)患者停用程序性死亡蛋白1(PD-1)或程序性死亡配体1(PD-L1)抑制剂后的后续治疗及疾病转归。

患者与方法

我们进行了一项回顾性分析,以检查晚期UC患者接受PD-1/PD-L1抑制剂治疗后的转归及全身治疗情况。从参与研究的机构收集人口统计学数据及所给予的治疗信息。进行单变量Cox回归分析,以检查与PD-1/PD-L1抑制剂治疗后总生存期(OS)潜在相关的临床因素。

结果

来自4个机构的62例患者的数据可供分析,记录了检查点抑制剂免疫治疗后的后续治疗及转归情况。患者中位年龄为65.5岁,51例(82.3%)为男性。55例有该数据的患者中,PD-1/PD-L1抑制剂治疗的中位(范围)持续时间为64(7-669)天。其中,22例(35.5%)患者在PD-1/PD-L1抑制剂治疗后接受了多种不同的化疗方案(n = 16)、化学生物联合治疗(n = 1)、生物制剂治疗(n = 4)及免疫治疗(n = 1)。从最后一次PD-1/PD-L1抑制剂治疗到后续治疗的中位(范围)时间为58(14-242)天。所有患者完成PD-1/PD-L1抑制剂治疗后的中位OS为149天(95%置信区间[CI]:75-359)。在接受了一些PD-1/PD-L1抑制剂治疗后的患者中,中位OS为182天(95%CI:121-372),从开始PD-1/PD-L1治疗后的中位疾病进展时间为124天(95%CI:61-273)。在这22例患者中,与OS相关的唯一显著基线预后因素是体能状态。

结论

在该数据集中,35.5%的晚期UC患者在接受PD-1/PD-L1抑制剂挽救治疗后接受了全身治疗。后续治疗后的转归似乎与既往未接受过PD-1/PD-L1抑制剂治疗的患者所观察到的转归相似。有必要对接受PD-1/PD-L1抑制剂治疗后的患者进行进一步研究,以确定与转归相关的因素及潜在的协同治疗顺序。

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