Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study.
Efficacy and Safety of Anti-PD-1 Plus Anlotinib in Patients With Advanced Non-Small-Cell Lung Cancer After Previous Systemic Treatment Failure-A Retrospective Study.
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抗 PD-1 加安罗替尼治疗既往全身治疗失败后晚期非小细胞肺癌患者的疗效和安全性——一项回顾性研究
DOI：
10.3389/fonc.2021.628124
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发表时间：
2021
影响因子：
4.7
通讯作者：
Teng F
中科院分区：
文献类型：
--
作者：
Wang P;Fang X;Yin T;Tian H;Yu J;Teng F
临床前和临床证据支持同时阻断程序性死亡-1（PD-1）和血管内皮生长因子受体（VEGFR）可增强抗原特异性T细胞迁移，并显示出患者可耐受的毒性和良好的抗肿瘤活性。在这项研究中，我们的目的是评估安洛替尼，一种新型的多靶点酪氨酸激酶抑制剂VEGFR，血小板衍生生长受体（PDGFR）和干细胞因子受体（c-Kit），与抗PD-1治疗晚期NSCLC患者的安全性和疗效。在IRB批准的研究中回顾性入组了67例既往接受过抗PD-1药物联合安洛替尼治疗的晚期NSCLC患者。每两周或三周施用抗PD-1药剂，包括派姆单抗、纳武单抗、坎雷珠单抗、托立帕利单抗、辛替利单抗和tislelizumab，直到达到疾病进展或不可接受的毒性。安洛替尼在21天周期的第1-14天口服给药，每日一次。通过不良事件的发生率评估联合治疗的安全性和耐受性。通过肿瘤反应和生存率评估治疗的疗效。中位随访期为8.7个月，85%（57/67）的患者发生了治疗相关不良事件，27例患者（40%）发生了3-4级不良事件。未观察到非预期不良事件或显著增加的毒性。未观察到完全缓解，19例患者部分缓解（28.4%），39例患者病情稳定（58.2%），9例患者病情进展（13.4%）。总有效率（ORR）和疾病控制率（DCR）分别为28.4%和86.6%。中位无进展生存期（PFS）为6.9个月（95% CI，5.5-8.3个月），总生存期（OS）为14.5个月（95% CI，10.9-18.1个月）。在EGFR突变阳性、肝转移和脑转移的患者中也观察到抗PD-1加安洛替尼的获益。在既往接受过治疗的晚期NSCLC患者中，抗PD-1治疗联合安洛替尼具有可耐受的毒性和良好的抗肿瘤活性。我们的研究结果增加了越来越多的证据，支持免疫治疗与抗血管生成药物相结合的好处。由于在联合治疗中未观察到额外的毒性，因此可以在联合或不联合化疗的情况下进一步评价该联合治疗。
Pre-clinical and clinical evidences support that simultaneous blockade of programmed death-1 (PD-1) and vascular endothelial growth factor receptor (VEGFR) can enhance antigen-specific T-cell migration, and show tolerable toxicity with favorable antitumor activity in patients. In this study, we aimed to assess the safety and efficacy of anlotinib, a novel multitarget tyrosine kinase inhibitor for VEGFR, platelet-derived growth receptor (PDGFR), and the stem cell-factor receptor (c-Kit), combined with anti-PD-1 treatment in patients with advanced NSCLC. Sixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib were retrospectively enrolled in an IRB approved study. Anti-PD-1 agents including pembrolizumab, nivolumab, camrelizumab, toripalimab, sintilimab, and tislelizumab were administered every two or three weeks until disease progression or unacceptable toxicity was reached. Anlotinib was administered orally once daily on days 1–14 of a 21-day cycle. The safety and tolerability of the combination treatment were assessed by the incidence of adverse events. The efficacy of the treatment was assessed by the tumor response and survival. With a median follow-up period of 8.7 months, treatment-related adverse events occurred in 85% (57/67) of patients and grade 3–4 adverse events were observed in 27 patients (40%). No unexpected adverse events or significantly increased toxicities were observed. Complete response was not observed, 19 patients had partial response (28.4%), 39 had stable disease (58.2%) and 9 had progressive disease (13.4%). The overall response (ORR) and disease control rates (DCR) were 28.4% and 86.6%, respectively. The median progression-free survival (PFS) was 6.9 months (95% CI, 5.5-8.3 months) and overall survival (OS) was 14.5 months (95% CI, 10.9-18.1 months). The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases. Anti-PD-1 treatment concomitant with anlotinib has tolerable toxicity and favorable antitumor activity in patients with previously treated advanced NSCLC. Our results add to the growing evidence that supports the benefits of combining immunotherapy with antiangiogenic drugs. This combination could be further evaluated with or without chemotherapy, since no additional toxicity was observed in the combination treatment.
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改善癌症免疫治疗的免疫血管串扰
DOI：
10.1038/nri.2017.145
发表时间：
2018-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Huang Y;Kim BYS;Chan CK;Hahn SM;Weissman IL;Jiang W
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影响因子：
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51.1
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82.9
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Melder, RJ;Koenig, GC;Jain, RK
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Jain, RK
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76.2
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Reck, Martin;Mok, Tony S. K.;Socinski, Mark A.
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Socinski, Mark A.