Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial.
Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial.
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Pembrolizumab治疗晚期骨肉瘤：一项单臂、开放标签、2期试验的结果
DOI：
10.1007/s00262-021-02876-w
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Palmerini E
中科院分区：
文献类型：
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作者：
Boye K;Longhi A;Guren T;Lorenz S;Næss S;Pierini M;Taksdal I;Lobmaier I;Cesari M;Paioli A;Løndalen AM;Setola E;Hompland I;Meza-Zepeda LA;Sundby Hall K;Palmerini E
目的：评价PD-1抗体培溴利珠单抗治疗成人晚期骨肉瘤的活性和安全性。这项研究是一项针对不能切除的复发性骨肉瘤患者的单臂、开放标签、2期试验。主要终点是治疗18周时的临床受益率(CBR)，使用RECIST v1.1定义为完全缓解、部分缓解或稳定疾病。这项试验采用西蒙-S两阶段设计，在第一阶段临床受益的12名患者中， ≥ 3被要求进入第二阶段。该试验在ClinicalTrials.gov注册，编号为NCT03013127。纳米串分析用于探索肿瘤基因的表达特征和途径。12名患者入选并接受研究治疗。在治疗18周时没有患者获得临床益处，患者在第一阶段完成后停止登记。估计的中位无进展生存期为1.7个月(95%可信区间1.2-2.2)。在数据截断时，有11名患者死于骨肉瘤。中位总生存期为6.6个月(95%可信区间3.8~9.3)。没有观察到与治疗相关的死亡或与药物相关的3级或4级不良事件。在11个可评估的肿瘤样本中，PD-L1的表达为阳性，该阳性样本来自一名混合治疗反应的患者。在这项晚期骨肉瘤的2期研究中，培溴利珠单抗耐受性良好，但没有显示出临床上显著的抗肿瘤活性。未来免疫调节剂治疗骨肉瘤的试验应该探索基于与反应相关的分子图谱选择的患者的联合策略。
To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2–2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8–9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.
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影响因子：
1.9
作者：
Tirtei, Elisa;Asaftei, Sebastian D.;Fagioli, Franca
通讯作者：
Fagioli, Franca
影响因子：
45.3
作者：
Bielack, Stefan S.;Kempf-Bielack, Beate;Juergens, Heribert
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Juergens, Heribert
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作者：
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通讯作者：
Ferrari S
影响因子：
8.4
作者：
Le Cesne, A.;Marec-Berard, P.;Italiano, A.
通讯作者：
Italiano, A.
影响因子：
3.1
作者：
Bacci, G;Briccoli, A;Picci, P
通讯作者：
Picci, P