Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study
Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study
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DOI：
10.1016/j.ejca.2019.07.018
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发表时间：
2019-09-01
影响因子：
8.4
通讯作者：
Italiano, A.
中科院分区：
文献类型：
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作者：
Le Cesne, A.;Marec-Berard, P.;Italiano, A.
目的：有一些证据表明免疫疗法在骨肉瘤患者的治疗中具有潜在的作用。患者和方法：这是一项开放标签、多中心、2期研究，派姆单抗联合节律环磷酰胺治疗晚期骨肉瘤患者。所有患者每隔一周服用50 mg环磷酰胺，并静脉注射200 mg派姆单抗（每3周一次）。有两个主要终点，根据实体肿瘤反应评估标准（RECIST） 1.1版，包括6个月时的非进展和客观反应。客观缓解率为20%和/或6个月无进展率为60%被确定为治疗有意义效果的合理目标。计划从患者肿瘤样本中进行免疫生物标志物的相关研究。结果：2015年10月13日至2017年7月3日，纳入17例患者。其中50例可评估疗效终点。4例患者肿瘤缩小，1例患者部分缓解（PR）（6.7%）。6个月无进展率为13.3%（95%置信区间[CI]: 1.7-40.5）。最常见的不良事件是1级或2级恶心、贫血、厌食和疲劳。程序性死亡配体1 （programmed death-ligand 1, PD-L1）表达率低，仅在14例肿瘤材料中观察到2例。唯一经历PR的患者是pd - l1阴性肿瘤。结论：抑制程序性细胞死亡1 （PD-1）在骨肉瘤中的作用有限。进一步研究PD-1抑制剂与调节微环境的药物的结合是必要的。(C) 2019 Elsevier Ltd.版权所有。
Purpose: There are some lines of evidence suggesting a potential role of immunotherapy for treating patients with osteosarcomas.Patients and methods: This was an open-label, multicentre, phase 2 study of pembrolizumab in combination with metronomic cyclophosphamide in patients with advanced osteosarcomas. All patients received 50 mg b.i.d. of cyclophosphamide one week on and one week off and 200 mg of intravenous pembrolizumab (every 3 weeks). There was a dual primary end-point, encompassing both the non-progression and objective responses at 6 months per Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1. An objective response rate of 20% and/or a 6-month non-progression rate of 60% were determined as reasonable objectives for treatment with meaningful effect. Correlative studies of immune biomarkers were planned from the patients' tumour samples.Results: Between October 13 2015 and July 3 2017, 17 patients were included. Fifty were assessable for the efficacy end-point. Four patients experienced tumour shrinkage, resulting in a partial response (PR) in one patient (6.7%). The 6-month non-progression rate was 13.3% (95% confidence interval [CI]: 1.7-40.5). The most frequent adverse events were grade I or II nausea, anaemia, anorexia and fatigue. programmed death-ligand 1 (PD-L1) expression rate was low, observed in only 2 cases of 14 with available tumour material. The only patient who experienced PR had a PD-L1-negative tumour.Conclusion: Programmed cell death 1 (PD-1) inhibition has limited activity in osteosarcomas. Further studies investigating PD-1 inhibitor in combination with agents modulating the microenvironment are warranted. (C) 2019 Elsevier Ltd. All rights reserved.