Antibiotics dim cancer immunotherapy outcomes

Cancer patients who have used antibiotics preceding the initiation of immune checkpoint inhibitors (ICIs) are likely to have unfavourable outcomes, as shown in the results of a meta-analysis.

Overall (OS) and progression-free (PFS) survival are shorter, with diminished response and faster disease progression, when compared with patients who did not receive antibiotics, according to a team of researchers from The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. However, they acknowledged that heterogeneity was substantial for all clinical outcomes.

The meta-analysis included 48 studies with a total population of 12,794 patients. The period of antibiotic exposure relative to ICI initiation ranged from 6 months before to 3 months after. All studies were of satisfactory to high quality and considered to have low risk of bias.

Pooled data showed that antibiotic exposure was associated with reduced OS (adjusted hazard ratio [aHR], 1.87, 95 percent confidence interval [CI], 1.55–2.25) and PFS (aHR, 1.93, 95 percent CI, 1.59–2.36), less frequent response to ICIs (odds ratio [OR], 0.54, 95 percent CI, 0.34–0.86), and higher incidence of disease progression (OR, 2.00, 95 percent CI, 1.27–3.14). [Int J Infect Dis 2021;106:142-154]

“However, the association with PFS was significantly more prominent in patients with melanoma or renal cell carcinoma (RCC) than nonsmall cell lung cancer (NSCLC). Also, the negative association with response rate and disease progression did not reach statistical significance in patients with NSCLC or melanoma,” the researchers noted.

They pointed out that the small number of patients and wide CIs in some subgroup analyses prevented them from drawing firm conclusions.

Regardless, “most patients with NSCLC have a smoking history and, hence, chronic obstructive pulmonary disease (COPD). Both COPD and the nature of NSCLC can increase the patient’s vulnerability to pulmonary infections, nosocomial pneumonia, and postobstructive pneumonia,” the researchers explained. So, the severity of such infections, which may benefit from aggressive antibiotic treatment, may have contributed to the observed differences.

“The absence of strong signals for response rate and disease progression in the NSCLC population may also be due to unique heterogeneity in the tumour micro-environment,” they added. “Furthermore, there seem to be differences in the baseline microbiome between RCC, melanoma, and NSCLC.”

Another thing worth noting, according to the researchers, is that although the associations between the use of antibiotics and OS, PFS, or response rate did not seem to be affected by timing, only antibiotic administration >1 month prior to ICI initiation was associated with increased disease progression. “This result merits further investigation, as it could indicate that relatively long timeframes are needed for changes in the intestinal microbiome to take place and interfere with the clinical efficacy of ICIs.”

In closing, the researchers highlighted the potential benefits of antimicrobial stewardship interventions, targeting patients with cancer who are receiving or will soon receive ICIs.

“Translational studies could help to identify a microbiome profile that is associated with favourable outcomes. Ultimately, these results may be helpful in designing novel therapeutic approaches, such as faecal microbiota transplantation, which could be of clinical benefit in this rapidly growing and vulnerable patient population,” they said.