College of Medicine and Public Health, Flinders University, Adelaide, Australia.
College of Medicine and Public Health, Flinders University, Adelaide, Australia; Department of Medical Oncology, Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Adelaide, Australia.
Eur Urol. 2020 Oct;78(4):540-543. doi: 10.1016/j.eururo.2020.06.061. Epub 2020 Jul 11.
Antibiotic effects on the gut microbiota may negatively impact survival with immune checkpoint inhibitors (ICIs). However, there is minimal evidence regarding whether antibiotic impacts are specific to ICIs or impacts in urothelial carcinoma (UC). In a post hoc analysis of IMvigor210 (single-arm atezolizumab) and IMvigor211 (phase III randomised trial of atezolizumab vs chemotherapy), the association between antibiotic use and overall survival (OS) and progression-free survival (PFS) was assessed via Cox proportional hazard analysis. Antibiotic use was defined as any antibiotic administration between 30 d prior to and 30 d after treatment initiation. Antibiotic use was associated with worse OS (n = 847, hazard ratio or HR [95% confidence interval {CI}] = 1.44 [1.19-1.73]) and PFS (1.24 [1.05-1.46]) with atezolizumab, but not chemotherapy (n = 415, 1.15 [0.91-1.46] and 1.09 [0.88-1.36], respectively). In the randomised cohort of IMvigor211, the OS treatment effect (HR [95% CI]) of atezolizumab versus chemotherapy was 0.95 (95% CI 0.71-1.25) for antibiotic users, compared with 0.73 (0.60-0.88) for nonusers (p[interaction] = 0.1). Similar associations were noted in the PD-L1 IC2/3 population. In conclusion, antibiotic use was associated with worse survival outcomes in UC patients treated with atezolizumab. The study does not justify a change in antibiotic selection for infections; however antibiotic overuse occurs in cancer care and this needs to be evaluated for ICIs. PATIENT SUMMARY: In this report from clinical trials IMvigor210 and IMvigor211, it was demonstrated that antibiotic use is consistently associated with worse survival in patients with urothelial carcinoma treated with atezolizumab. No antibiotic association was observed in patients treated with chemotherapy, suggesting that antibiotics may specifically reduce the effectiveness of cancer immunotherapies. Future research will continue to explore the effect of antibiotics on other immune checkpoint inhibitors and confirm whether immune checkpoint inhibitors remain the treatment of choice in cancer patients requiring antibiotics.
抗生素对肠道微生物群的影响可能会对免疫检查点抑制剂 (ICI) 的生存产生负面影响。然而，关于抗生素的影响是否特定于 ICI 或在尿路上皮癌 (UC) 中存在的证据很少。在 IMvigor210（单臂阿特珠单抗）和 IMvigor211（阿特珠单抗与化疗的 III 期随机试验）的事后分析中，通过 Cox 比例风险分析评估了抗生素使用与总生存期 (OS) 和无进展生存期 (PFS) 的关联。抗生素使用的定义为治疗开始前 30 天至治疗开始后 30 天之间的任何抗生素给药。与阿特珠单抗相比，抗生素使用与较差的 OS（n=847，风险比或 HR [95%置信区间 {CI}] =1.44 [1.19-1.73]）和 PFS（1.24 [1.05-1.46]）相关，但与化疗无关（n=415，分别为 1.15 [0.91-1.46] 和 1.09 [0.88-1.36]）。在 IMvigor211 的随机队列中，阿特珠单抗与化疗相比，抗生素使用者的 OS 治疗效果（HR [95%CI]）为 0.95（95%CI 0.71-1.25），而非使用者为 0.73（0.60-0.88）（p[交互] =0.1）。在 PD-L1 IC2/3 人群中也观察到了类似的关联。总之，在接受阿特珠单抗治疗的 UC 患者中，抗生素的使用与较差的生存结果相关。该研究并不能证明为感染选择抗生素需要改变；然而，抗生素在癌症治疗中被过度使用，这需要针对 ICI 进行评估。患者总结：在临床试验 IMvigor210 和 IMvigor211 的这份报告中，证明了在接受阿特珠单抗治疗的尿路上皮癌患者中，抗生素的使用与生存结果较差始终相关。在接受化疗的患者中未观察到抗生素的相关性，这表明抗生素可能会特异性降低癌症免疫疗法的有效性。未来的研究将继续探索抗生素对其他免疫检查点抑制剂的影响，并确认在需要抗生素的癌症患者中，免疫检查点抑制剂是否仍然是治疗的首选。
