Overuse of antibiotics may shorten survival in urothelial carcinoma
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The overprescribing and overuse of antibiotics has been scrutinized in recent years due to the threat of antimicrobial resistance.
Research has suggested up to 50% of antibiotics used in cancer treatments are prescribed inappropriately. This overuse does not appear to be benign: a study published in European Urology has found an association of antibiotic use with reduced rates of survival among patients with urothelial carcinoma who received the PD-L1 inhibitor atezolizumab (Tecentriq, Genentech).
“Seemingly from a perspective that there will be no adverse consequences, there is emerging evidence that antibiotics are often over/inappropriately prescribed in patients with cancer,” study author Ashley M. Hopkins, MD, research fellow at the College of Medicine and Public Health at Flinders University in Australia, said in an interview with Healio.
Hopkins and colleagues conducted a post-hoc analysis of the single-arm IMvigor210 and the randomized IMvigor211 trials in which atezolizumab was used to treat advanced urothelial carcinoma. The researchers assessed concomitant use of antibiotics in these trial populations through Cox proportional hazard analysis.
Hopkins spoke with Healio about the study’s findings and what they could mean for the stewardship of antibiotics in the treatment of patients with urothelial carcinoma and other cancers.
Question: Your study found shorter OS with antibiotic use specifically among patients with urothelial carcinoma who took atezolizumab. What drives this association?
Answer: Antibiotics cause significant gut microbiota changes. The gut microbiota plays an important role in regulating immune function, and there is a growing awareness that an altered gut microbiota may negatively impact immune checkpoint inhibitor (ICI) efficacy. Antibiotics are used by many patients with cancer, and the study hypothesized that antibiotics may be associated with a decrease in ICI efficacy.
Q: When would antibiotics be inappropriate for use by patients with cancer?
A: As an example, one study indicated that nearly one-third of hematology-oncology outpatients had been prescribed antibiotics for upper respiratory infections, despite viral etiologies identified among 75% of those tested.
Q: You observed no similar association between antibiotic use and chemotherapy. Why do you think chemotherapy does not appear to have this effect?
A: ICIs remove inhibitory T-cell activation signals, enabling tumor-reactive T cells to overcome regulatory mechanisms and mount effective antitumor response. The gut microbiota also plays an important role in regulating homeostasis and immune function, and an impacted gut microbiota can negatively affect the ability of ICIs to activate the immune system.
Q: Should patients with urothelial carcinoma who are prone to infection be ruled out as candidates for ICIs like atezolizumab? Are there other immune therapies that do not have negative effects on survival?
A: The main clinical implication of our study is to highlight the need for a cautious approach to antibiotics during immunotherapy and clearer guidelines with respect to what are critical and noncritical antibiotics.
The interaction test was not statistically significant. Consequently, there is no evidence that the antibiotic-use subgroup is statistically associated with less OS benefit from atezolizumab (vs. chemotherapy) than the nonantibiotic-use subgroup. Nonetheless, the original study was not powered to assess the subgroup, so the findings of our study exemplify an urgent need for further study. This association has not been evaluated in other randomized controlled trials of other ICIs.
References:
- Hopkins AM, et al. Eur Urol. 2020;doi:10.1016/j.eururo.2020.06.061.
- Krantz EM, et al. Clin Infect Dis. 2020;doi:10.1093/cid/ciz409.
For more information:
Ashley M. Hopkins, MD, can be reached at ashley.hopkins@flinders.edu.au.
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