Antibiotic Use Associated with Worse Survival in Patients with Urothelial Carcinoma
In this study, antibiotic use was consistently associated with worse survival outcomes in patients with urothelial carcinoma treated with atezolizumab, but not chemotherapy.
According to a report from clinical trials IMvigor210 and IMvigor211 published in European Urology, antibiotic use was consistently associated with worse survival outcomes in patients with urothelial carcinoma treated with atezolizumab (Tecentriq).1
Additionally, no antibiotic association was observed in patients treated with chemotherapy, indicating that antibiotics may specifically reduce the effectiveness of immunotherapies for cancer.
"These results provide strong justification for prospective studies to tease out whether antibiotics are primarily a surrogate of an unfit or immunodeficient patient or whether antibiotic effects on the gut microbiota are having casual impacts on [immune checkpoint inhibitor; ICI] efficacy," Ashley Hopkins, PhD, National Breast Cancer Foundation of Australia postdoctoral fellow working in the Precision Medicines Group at the Flinders Centre for Innovation in Cancer at Flinders University, said in a press release.2 "If the latter is true, in patients at a high risk of recurrent infections, it may need to be considered whether ICI therapy is the most appropriate way to go."
In this post hoc analysis of IMvigor210, a single arm study of atezolizumab, and IMvigor211, a phase 3 randomized trial of atezolizumab vs chemotherapy, researchers assessed the association between antibiotic use, overall survival (OS), and progression-free survival (PFS).
Ultimately, antibiotic use was associated with worse OS (n = 847; HR, 1.44; 95% CI, 1.19-1.73) and PFS (HR, 1.24; 95% CI, 1.05-1.46) with atezolizumab, but not chemotherapy (n = 415; HR, 1.15; 95% CI, 0.91-1.46; and HR, 1.09; 95% CI, 0.88-1.36, respectively). Specifically, in the randomized cohort of IMvigor211, the OS treatment effect of atezolizumab versus chemotherapy was 0.95 (95% CI, 0.71-1.25) for antibiotic users, compared with 0.73 (95% CI, 0.60-0.88) for nonusers (P [interaction] = .1). Further, similar associations were observed in a population of patients with PD-L1 expression on at least 5% of tumor-infiltrating immune cells (IC2/3).
“This study is the first to provide evidence that antibiotics, which impact the gut microbiota, have substantial associations with out-comes for ICIs used in [urothelial carcinoma],” the authors explained. “Antibiotic effects on the urinary microbiota may also be important.”
However, the researchers explained that this study was limited in its ability to provide evidence on the effect of antibiotic duration, type, or indication, which they indicated should continue to be explored. In addition, the study had a restricted range of ICIs and evaluation settings, therefore future research should expand upon the range of ICIs and cancer types studied.
“This post hoc analysis does not justify a change in antibiotic selection for bacterial infections, as these infections need to continue to be treated properly,” the authors noted. “However, research indicates that overuse of antibiotics in cancer care occurs, and in addition to increasing potential risks of resistant bacterial infections, this study’s findings suggest a need for extra caution when an ICI is being used.”
References:
1. Hopkins AM, Kichenadasse G, Karapetis CS, Rowland A, Sorich MJ. Concomitant Antibiotic Use and Survival in Urothelial Carcinoma Treated with Atezolizumab. European Urology. doi: 10.1016/j.eururo.2020.06.061
2. Antibiotic overuse reduces bladder cancer survival rates [news release]. Flinders University. Published August 16, 2020. Accessed September 8, 2020. https://www.eurekalert.org/pub_releases/2020-08/fu-aor081620.php
