The Christie NHS Foundation Trust, Manchester, United Kingdom.
Cancer Research UK Manchester Institute, Manchester, United Kingdom.
Oncologist. 2020 Jan;25(1):55-63. doi: 10.1634/theoncologist.2019-0160. Epub 2019 Jul 10.
With the advent of immunotherapy, substantial progress has been made in improving outcomes for patients with advanced cancer. However, not all patients benefit equally from treatment, and confounding immune-related issues may have an impact. Several studies suggest that antibiotic use (which alters the gut microbiome) may result in poorer outcomes for patients treated with immune checkpoint inhibitors (ICI).
This is a large, single-site retrospective review of n = 291 patients with advanced cancer treated with ICI (n = 179 melanoma, n = 64 non-small cell lung cancer, and n = 48 renal cell carcinoma). Antibiotic use (both single and multiple courses/prolonged use) during the periods 2 weeks before and 6 weeks after ICI treatment was investigated.
Within this cohort, 92 patients (32%) received antibiotics. Patients who did not require antibiotics had the longest median progression-free survival (PFS), of 6.3 months, and longest median overall survival (OS), of 21.7 months. With other clinically relevant factors controlled, patients who received a single course of antibiotics had a shorter median OS (median OS, 17.7 months; p = .294), and patients who received multiple courses or prolonged antibiotic treatment had the worst outcomes overall (median OS, 6.3 months; p = .009). Progression-free survival times were similarly affected.
This large, multivariate analysis demonstrated that antibiotic use is an independent negative predictor of PFS and OS in patients with advanced cancer treated with ICIs. This study highlighted worse treatment outcomes from patients with cumulative (multiple or prolonged courses) antibiotic use, which warrants further investigation and may subsequently inform clinical practice guidelines advocating careful use of antibiotics.
Antibiotic use is negatively associated with treatment outcomes of immune checkpoint inhibitors (ICI) in advanced cancer. Cumulative antibiotic use is associated with a marked negative survival outcome. Judicious antibiotic prescribing is warranted in patients receiving treatment with ICI for treatment of advanced malignancy.
随着免疫疗法的出现，晚期癌症患者的治疗效果取得了显著进展。然而，并非所有患者都能从治疗中同等获益，免疫相关的混杂因素可能会产生影响。一些研究表明，抗生素的使用（改变肠道微生物群）可能会导致接受免疫检查点抑制剂（ICI）治疗的患者预后较差。
这是一项大型、单站点回顾性研究，纳入了 291 名接受 ICI 治疗的晚期癌症患者（179 名黑色素瘤、64 名非小细胞肺癌和 48 名肾细胞癌）。研究调查了 ICI 治疗前 2 周和治疗后 6 周期间抗生素的使用情况（包括单疗程和多疗程/长期使用）。
在该队列中，92 名患者（32%）接受了抗生素治疗。未使用抗生素的患者无进展生存期（PFS）最长，为 6.3 个月，总生存期（OS）最长，为 21.7 个月。在控制其他具有临床意义的因素后，接受单疗程抗生素治疗的患者 OS 中位数较短（中位 OS，17.7 个月；p =.294），而接受多疗程或长期抗生素治疗的患者总体预后最差（中位 OS，6.3 个月；p =.009）。PFS 时间也受到类似影响。
这项大型、多变量分析表明，抗生素的使用是接受 ICI 治疗的晚期癌症患者 PFS 和 OS 的独立负预测因素。本研究强调了累积（多疗程或长期疗程）抗生素使用的患者治疗结局更差，这需要进一步研究，并可能随后为支持谨慎使用抗生素的临床实践指南提供依据。
抗生素的使用与晚期癌症患者接受免疫检查点抑制剂（ICI）治疗的疗效结果呈负相关。累积抗生素使用与显著的生存不良结局相关。在接受 ICI 治疗晚期恶性肿瘤的患者中，应慎重使用抗生素。
