Safety and efficacy of PD-1 blockade-activated multiple antigen-specific cellular therapy alone or in combination with apatinib in patients with advanced solid tumors: a pooled analysis of two prospective trials
Safety and efficacy of PD-1 blockade-activated multiple antigen-specific cellular therapy alone or in combination with apatinib in patients with advanced solid tumors: a pooled analysis of two prospective trials
复制标题
PD-1阻断激活的多抗原特异性细胞疗法单独或与阿帕替尼联合治疗晚期实体瘤患者的安全性和有效性：两项前瞻性试验的汇总分析
DOI：
10.1007/s00262-019-02375-z
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发表时间：
2019-09-01
影响因子：
5.8
通讯作者：
Jiang, Xiaodong
中科院分区：
文献类型：
--
作者：
Liang, Lijun;Wen, Yixuan;Jiang, Xiaodong
背景体外阻断PD-1和血管内皮生长因子受体2抑制剂（阿帕替尼）可增强多抗原特异性细胞治疗（MASCT）的致死效应。我们分析了来自我们的I/II期试验的汇总数据，以确定PD-1阻断（SHR-1210）激活的MASCT（aMASCT）单独或与阿帕替尼联合治疗晚期实体瘤的毒性和功效。n=38）。安全性是主要终点。次要终点为抗肿瘤反应、无进展生存期（PFS）和总生存期（OS）。结果aMASCT组和aMASCT+阿帕替尼组分别有18/32（56.3%）和25/38（65.8%）例患者发生治疗相关不良事件（AE）。未报告严重AE，阿帕替尼未增加免疫治疗相关毒性。与aMASCT组相比，aMASCT+阿帕替尼组的客观缓解率（34.2%和18.8%）和PFS（中位数6.0和4.5个月，P=0.002）有所改善;但是，OS没有改善（中位数10.0和8.2个月，P=0.098）。多因素分析显示，两个或两个以上周期的aMASCT治疗是PFS和OS的独立和有利的预后因素。两组患者在一个周期的aMASCT治疗后，循环T细胞增加，TcB降低。结论aMASCT联合阿帕替尼治疗晚期实体瘤安全有效。
Background The lethal effects of multiple antigen-specific cellular therapy (MASCT) may be enhanced by blocking PD-1 in vitro and vascular endothelial growth factor receptor 2 inhibitor (apatinib). We analyzed the pooled data from our phase I/II trials to determine the toxicity and efficacy of PD-1 blockade (SHR-1210)-activated MASCT (aMASCT) alone or in combination with apatinib in advanced solid tumors.Methods Patients with advanced solid tumors received aMASCT alone (n=32) or aMASCT plus apatinib (500 mg q.d., n=38) after standard treatment. The safety profile was the primary end point. The secondary end points were antitumor response, progression-free survival (PFS), and overall survival (OS). The circulating T cells were quantified before and after aMASCT infusion.Results Treatment-related adverse events (AEs) occurred in 18/32 (56.3%) and 25/38 (65.8%) patients in the aMASCT and aMASCT plus apatinib groups, respectively. No serious AEs were reported, and apatinib did not increase immunotherapy-related toxicity. The objective response rate (34.2% and 18.8%) and PFS (median 6.0 and 4.5 months, P=0.002) were improved in the aMASCT plus apatinib group compared with the aMASCT group; however, the OS was not improved (median 10.0 and 8.2 months, P=0.098). Multivariate analyses indicated that two or more cycles of aMASCT treatment was an independent and favorable prognostic factor of PFS and OS. The circulating T cells increased and Tregs decreased in both groups after one cycle of aMASCT treatment.Conclusions Treatment with aMASCT plus apatinib was safe and effective for the management of advanced solid tumors.