Timing is everything… especially when it has to do with antibiotic treatment in relation to immunotherapy. A study that was carried out by researchers at Imperial College London shows just how important timing with this matter can be, and how drastic of an influence it can have on a person’s survival time. Almost 200 cancer patients on immunotherapy participated in the study and all of them fared worse if they had recently taken antibiotics, with their response and overall survival rate ‘crashing.’
The participants were taking a type of immunotherapy called checkpoint inhibitors, part of the standard treatment pathway for cancer patients on the NHS. Those who received broad-spectrum antibiotics within the month prior to starting immunotherapy had a significantly worse response to treatment – it resulted in lower overall survival rates and higher chances of the patients’ cancers progressing. However, this was not the case with those who received antibiotics alongside the immunotherapy or not at all. The prospective study has been published in the journal JAMA Oncology.
Dr. David Pinato, from Imperial’s Department of Surgery & Cancer and corresponding author of the study, said:
Cancer immunotherapy can be successful in around 20% of patients, but it’s very difficult to predict who is going to respond. This work adds further evidence that antibiotics have an impact. We have shown that with prior antibiotic exposure, patients’ response to immunotherapy and survival crashes.
The researchers speculate that antibiotics before immunotherapy disrupts the balance of bacteria and microbes in the gut (the microbiome) thus reducing the diversity of bacteria present. This, in turn, impacts the immune system, weakening the body’s immune response.
This study highlights the importance of the need for further studies to understand the mechanisms at play. The results of this study could potentially influence clinical practice in regards to requiring a higher threshold for giving antibiotics to cancer patients starting immunotherapy. It could also lead to the development of diverse probiotics to increase cancer survival rates.
Dr. Pinato explained:
We know that giving patients antibiotics affects their microbiome and increasingly, the evidence shows it influences treatment outcomes. It is important that patients who need antibiotics to treat bacterial infections receive the drugs they need. But these findings urge for more care in the decision-making process for some patients. It raises questions of whether we need a higher threshold for antibiotic prescribing in cancer patients due to receive immunotherapy.
The Study
- 196 patients being treated at Imperial College Healthcare and Chelsea and Westminster Hospital NHS Trusts participated. They were all receiving immunotherapy as part of their routine care on the NHS.
- The specific type of immunotherapy (there are various) was a treatment using immune checkpoint inhibitors – a therapy which disrupts the ability of cancer cells to ‘hide’ themselves, enabling the body’s immune cells to target and destroy tumors.
- Disease types included non-small cell lung cancer, melanoma, head and neck cancer, carcinomas and other types of cancer.
- Patients were categorized in three groups, those that received broad-spectrum antibiotics up to 30 days prior to beginning their immunotherapy treatment, those that received antibiotics during their therapy, and those that did not take them at all. (Of those that received antibiotics, respiratory infections were the most common cause for prescription.)
- Class of antibiotic used included beta-lactams, quinolones, macrolides, sulphonamides, tetracyclines, aminoglycosides, and nitroimidazole.
The Results
- 26 patients received antibiotics prior to immunotherapy – their median overall survival was 2 months. They were less likely to be responsive to therapy and their primary disease was nearly twice as likely to progress.
- 68 patients received antibiotics during their immunotherapy – their median overall survival rate was similar to those that did not take antibiotics.
- 102 patients did not take antibiotics – their median overall survival was 26 months.
- These effects were seen similarly across all cancer types.
- The effect was also independent of the class of antibiotic used.
- Patients with prior antibiotic use were likely to be less responsive to immunotherapy, with their primary disease almost twice as likely to progress.
- The effect had nothing to do with the class of antibiotic used.
Conclusion
This study had its limitations, such as the small number of patients, and a lack of direct observations of changes to the gut microbiome. In addition, this study couldn’t get into the impact that any other health conditions might have had on the patients’ survival. Nevertheless, they are confident of the link and the need for further studies to expand on these findings. However, more research is required to understand the mechanism behind the reduced response and drop off in overall survival.
For the next phase of their studies, the researchers plan to see what impact, if any, prior antibiotic use is having on the microbiome of patients with a follow-up observational clinical trial funded by the NIHR Imperial Biomedical Research Centre. These future studies may involve an investigation into whether re-balancing or augmenting the microbiome could improve patient outcomes.
