Ann Oncol:RCC和NSCLC:抗生素使免疫检查点抑制剂的疗效大打折扣

2018-07-19 张琪 环球医学网

与化疗和靶向治疗等手段相比,免疫检查点抑制剂(ICI)起效的机制,在于重新激活癌症患者体内的免疫细胞,发挥它们强大的杀伤力,在临床治疗中屡屡上演绝地反击,治愈原有手段无济于事的患者的奇迹。但2018年6月,发表在《Ann Oncol》的一项研究显示,抗生素(ATB)可通过改变肠道菌群多态性和组成,造成生态失调,从而使ICI的疗效大打折扣。

与化疗和靶向治疗等手段相比,免疫检查点抑制剂(ICI)起效的机制,在于重新激活癌症患者体内的免疫细胞,发挥它们强大的杀伤力,在临床治疗中屡屡上演绝地反击,治愈原有手段无济于事的患者的奇迹。但2018年6月,发表在《Ann Oncol》的一项研究显示,抗生素(ATB)可通过改变肠道菌群多态性和组成,造成生态失调,从而使ICI的疗效大打折扣。

肠道菌群的组成可影响癌症患者ICI治疗后的抗肿瘤免疫应答以及临床前和临床结局。而抗生素(ATB)可改变肠道菌群多态性和组成,造成生态失调,从而影响ICI的有效性。

研究者在2家学术机构检测了接受抗程序性细胞死亡配体-1单克隆抗体单药治疗或联合治疗的晚期肾细胞癌(RCC)和非小细胞肺癌NSCLC)患者。在开始ICI后30天内接受ATB的患者与未接受ATB的患者进行比较。通过RECIST1.1确定客观应答率、无进展生存期(PFS),并评估总生存期(OS)。

16/121名(13%)RCC患者和48/239名(20%)NSCLC患者接受ATB。最常见的ATB为β-内酰胺或喹诺酮类药物,以治疗肺炎或尿路感染

在RCC患者中,与未接受ATB相比,接受ATB治疗者与主要疾病进展(PD)增加(75% vs 22%)、PFS缩短(中位1.9 vs 7.4个月)、OS缩短(中位17.3 vs 30.6个月)相关。

在NSCLC患者中,是否接受ATB治疗的主要PD发生率相似,但是接受ATB与PFS(中位1.9 vs 3.8个月,p=0.03)和OS(中位7.9 vs 24.6个月,p<0.01)的减少相关。

在多变量分析中,ATB仍然对RCC患者的PFS和NSCLC患者的OS有显着的影响。

作者认为,ATB与RCC和NSCLC患者ICI的临床获益减少相关。调节ATB相关的微生物失调和肠道菌群组成是改善ICI的临床结局的有效策略。

免疫检查点抑制剂改写了肿瘤治疗的历史,将晚期肿瘤的药物治疗向前推进了一大步。晚期肿瘤患者治疗能有这样的进步着实不易,千万不能因抗生素的使用这点小的失误使来之不易的疗效因此折损。

原始出处:
L Derosa M D Hellmann M Spaziano,et al.Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer.Annals of Oncology, Volume 29, Issue 6, 1 June 2018, Pages 1437–1444, https://doi.org/10.1093/annonc/mdy103

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    2018-10-31 jklm09
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    2019-04-09 isabellayj
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    2018-12-06 minlingfeng
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    2018-07-20 1ddf0692m34(暂无匿称)

    学习了,长知识

    0

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    2018-07-19 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

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    2018-07-19 1ddf0692m34(暂无匿称)

    学习了,长知识

    0

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