Antibiotic use is associated with worse survival in patients with urothelial carcinoma treated with immunotherapy, an Australian study has found

Analysis of outcomes for patients involved in two clinical trials – IMvigor210 and IMvigor211 – found that recent antibiotic use (within 30 days) was associated with worse overall survival (hazard ratio 1.44) and progression free survival (HR 1.24) in 847 patients treated with atezolizumab, but not in 415 patients treated with chemotherapy ( HR 1.15).

The findings reported in European Urology, are not proof of a causal association but add further weight to suggestions that antibiotics may directly affect the efficacy of immunotherapy, according to researchers from Flinders University, Adelaide.

While it is possible that antibiotic use may be a prognostic marker for poorer health status, the fact that no effect was seen in patients treated with chemotherapy raised the possibility of an interaction with immunotherapy, said Dr Ashley Hopkins and colleagues

In their article they said antibiotics would alter the gut microbiota, which plays an important role in regulating homoeostasis and immune function, and thus antibiotics may negatively impact systemic immune response and immune checkpoint inhibitor (ICI) efficacy via the microbiota.

They noted that their findings were in line with another recent study that showed a significant negative prognostic association of antibiotic use on overall survival in advanced non–small-cell lung cancer treated with atezolizumab, with no significant association for docetaxel.

“The consistency in findings exemplifies an urgent need for a comprehensive pooled analysis of all immune checkpoint inhibitor randomised clinical trials to determine conclusively whether antibiotics influence immune checkpoint inhibitor efficacy or they are simply a prognostic marker for many treatments,” they said

“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,” they added.

“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 immune checkpoint inhibitor is being used.”