Gaucher Louis, Adda Leslie, Séjourné Alice, Joachim Camille, Guillaume Chaby, Poulet Claire, Liabeuf Sophie, Gras-Champel Valérie, Masmoudi Kamel, Houessinon Aline, Bennis Youssef, Batteux Benjamin
Department of Clinical Pharmacology, Amiens University Medical Center, Amiens, France.
Department of Rheumatology, Saint-Quentin Medical Center, Saint-Quentin, France.
Ther Adv Med Oncol. 2021 Mar 15;13:17588359211000591. doi: 10.1177/17588359211000591. eCollection 2021.
There are conflicting data on the effects of dysbiosis-inducing drugs, and especially antibiotics (ATBs), on clinical outcomes in patients treated with immune checkpoint inhibitors (ICIs). There is a particular lack of data for patients with melanoma.
We performed a single-center retrospective study of the associations between ATBs and other drugs known to modify the gut microbiota (proton pump inhibitors, nonsteroidal anti-inflammatory drugs, statins, opioids, anti-vitamin K, levothyroxine, vitamin D3, antiarrhythmics, metformin and phloroglucinol), overall survival (OS) and tumor response in consecutive cancer patients (particularly those with melanoma) treated with an ICI (ipilimumab, nivolumab or pembrolizumab) over a 9-year period.
A total of 372 patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Overall, 112 patients (30.1%) had received ATBs. ATB use was associated with (1) shorter OS in the study population as a whole [adjusted hazard ratio [95% confidence interval (CI)]: 1.38 (1.00-1.90), = 0.048] and in patients with melanoma [adjusted hazard ratio (95% CI): 2.60 (1.06-6.39), = 0.037], and (2) a lower response rate in the study population as a whole [8.1%, 31.1% in patients not treated with ATBs; adjusted odds ratio (95% CI): 6.06 (2.80-14.53), < 0.001] and in patients with melanoma [adjusted odds ratio (95% CI): 4.41 (1.04-22.80), = 0.045]. Sensitivity analyses that minimized the indication bias did not reveal an association between OS and the presence of an infection requiring ATBs (quantified as the severity of infection, hospitalization for an infection, or ICI discontinuation). Other dysbiosis-inducing drugs were not associated with a difference in OS.
Unlike other dysbiosis-inducing drugs, ATBs were associated with poorer clinical outcomes in ICI-treated patients overall and in the subset of patients with melanoma.
关于导致菌群失调的药物，尤其是抗生素（ATB）对接受免疫检查点抑制剂（ICI）治疗患者临床结局的影响，现有数据相互矛盾。黑色素瘤患者的数据尤为缺乏。
我们进行了一项单中心回顾性研究，探讨ATB与其他已知可改变肠道微生物群的药物（质子泵抑制剂、非甾体抗炎药、他汀类药物、阿片类药物、维生素K拮抗剂、左甲状腺素、维生素D3、抗心律失常药、二甲双胍和间苯三酚）、总生存期（OS）以及在9年期间接受ICI（伊匹木单抗、纳武单抗或帕博利珠单抗）治疗的连续癌症患者（尤其是黑色素瘤患者）的肿瘤反应之间的关联。
共纳入372例患者。平均年龄±标准差为64.0±12.1岁。最常处方的ICI是纳武单抗（58.3%的患者），最常见的适应证是肺癌（44.6%）和黑色素瘤（29.6%）。总体而言，112例患者（30.1%）接受过ATB治疗。使用ATB与以下情况相关：（1）在整个研究人群中OS较短[调整后风险比[95%置信区间（CI）]：1.38（1.00 - 1.90），P = 0.048]，在黑色素瘤患者中也是如此[调整后风险比（95% CI）：2.60（1.06 - 6.39），P = 0.037]；（2）在整个研究人群中缓解率较低[8.1%，未接受ATB治疗的患者为31.1%；调整后优势比（95% CI）：6.06（2.80 - 14.53），P < 0.001]，在黑色素瘤患者中也是如此[调整后优势比（95% CI）：4.41（1.04 - 22.80），P = 0.045]。将指征偏倚降至最低的敏感性分析未发现OS与需要使用ATB的感染（根据感染严重程度、因感染住院或停用ICI进行量化）之间存在关联。其他导致菌群失调的药物与OS差异无关。
与其他导致菌群失调的药物不同，ATB与接受ICI治疗的患者总体以及黑色素瘤患者亚组中较差的临床结局相关。
