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PD1 抑制剂治疗晚期肉瘤的活性:一项单中心回顾性分析。

Activity of PD1 inhibitor therapy in advanced sarcoma: a single-center retrospective analysis.

机构信息

The Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA.

Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W 10th Ave, Columbus, OH, 43210, USA.

出版信息

BMC Cancer. 2020 Jun 5;20(1):527. doi: 10.1186/s12885-020-07021-x.

Abstract

BACKGROUND

Sarcomas constitute a heterogeneous group of tumors with different clinical behaviors and variable responses to systemic therapies. Recent immunotherapy studies with PD1 inhibitors (PD1i) show promising results with use in certain soft-tissue sarcomas; however, the clinical and molecular features that best predict response to PD1i remain unclear.

METHODS

Demographic, imaging, histologic, and genetic sequencing data was collected for sarcoma patients who received nivolumab or pembrolizumab (PD1i) treatment at our institution between January 1st 2015 and April 23rd 2018. The primary objective was to determine progression-free survival (PFS) in patients with advanced sarcomas receiving PD1i. Secondary objectives included determining overall survival (OS) and assessment of characteristics associated with response to PD1i. Fifty-six patients who were treated with PD1i therapy met inclusion criteria for this study.

RESULTS

Partial response towards PD1i treatment was seen in 3 in 26 evaluable patients, but no complete responses were observed (overall response rate 11.5%). Within this group of patients, the 90 day PFS was found to be 48.8%. In patients in whom PD1 expression was known, there was a statistically significant positive correlation between expression of PD1 and longer PFS and OS rates. Patients that were treated with more than four cycles of PD1i therapy were also more likely to have a greater OS.

CONCLUSIONS

This study suggests activity of PD1i in a pretreated cohort of advanced sarcoma patients, particularly for the subset of patients with PD1 positive tumors. Our results highlight the importance of further research to better target the optimal patient population and markers of response.

摘要

背景

肉瘤是一组具有不同临床行为和对系统治疗反应不同的异质性肿瘤。最近使用 PD1 抑制剂(PD1i)进行的免疫治疗研究显示,在某些软组织肉瘤中具有良好的疗效,但最佳预测 PD1i 反应的临床和分子特征仍不清楚。

方法

收集了在我们机构接受纳武单抗或帕博利珠单抗(PD1i)治疗的肉瘤患者的人口统计学、影像学、组织学和基因测序数据,这些患者的治疗时间为 2015 年 1 月 1 日至 2018 年 4 月 23 日。主要目的是确定接受 PD1i 治疗的晚期肉瘤患者的无进展生存期(PFS)。次要目标包括确定总生存期(OS)和评估与 PD1i 反应相关的特征。56 名接受 PD1i 治疗的患者符合本研究的纳入标准。

结果

在 26 名可评估的患者中,有 3 名患者对 PD1i 治疗有部分反应,但没有完全反应(总反应率为 11.5%)。在这组患者中,90 天的 PFS 为 48.8%。在 PD1 表达已知的患者中,PD1 表达与更长的 PFS 和 OS 率之间存在统计学上的显著正相关。接受超过 4 个周期 PD1i 治疗的患者也更有可能有更长的 OS。

结论

这项研究表明 PD1i 在预处理的晚期肉瘤患者中具有活性,特别是对于 PD1 阳性肿瘤的亚组患者。我们的结果强调了进一步研究的重要性,以更好地确定最佳患者人群和反应标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f62/7275332/c74b44e0cd3c/12885_2020_7021_Fig1_HTML.jpg

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