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Antibiotics lower survival rates in cancer patients receiving immunotherapy | immuno Imperial news

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Antibiotics lower survival rates in cancer patients receiving immunotherapy | immuno Imperial news

Cancer patients undergoing immunotherapy do worse if they have recently taken antibiotics, with their response and overall survival ‘crash’.

The findings come from a study of nearly 200 cancer patients in the UK who were taking a type of immunotherapy called checkpoint inhibitors, part of the standard treatment for cancer patients on the NHS.

Researchers found that patients who received broad-spectrum antibiotics in the month prior to starting treatment had a significantly worse response to immunotherapy.

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Compared to patients who received antibiotics in addition to the immunotherapy or no antibiotics at all, antibiotic treatment before the immunotherapy was associated with lower overall survival rates and the patients’ cancers were more likely to progress.

Previous exposure to antibiotics stalls patient response to immunotherapy and survival loopt Dr David Pinato Department of Surgery & Cancer

The researchers suggest this may be because antibiotics disrupt the balance of bacteria and microbes in the gut, the microbiome, which in turn affects the immune system.

The prospective study, led by researchers from Imperial College London and published today in the journal JAMA Oncology, emphasizes the importance of the timing of antibiotic treatment and the need for further studies to understand the mechanisms at play.

The researchers say the findings could influence clinical practice, including a higher threshold for giving antibiotics to cancer patients starting immunotherapy.

Dr David Pinato, of Imperial’s Department of Surgery & Cancer and corresponding author of the study, said: “Cancer immunotherapy may be successful in about 20 percent of patients, but it is very difficult to predict who will respond. This work adds further evidence that antibiotics have an impact. We have shown that with previous exposure to antibiotics, patients’ response to immunotherapy and survival crashes.”

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IMMUNE RESPONSE

In the study, the team looked at 196 patients who received immunotherapy as part of their routine care on the NHS, and who were treated at Imperial College Healthcare and Chelsea and Westminster Hospital NHS Trusts.

The patients’ primary disease included non-small cell lung cancer, melanoma, head and neck cancer, carcinomas, and other cancers. All patients were treated with immune checkpoint inhibitors, a therapy that disrupts the ability of cancer cells to ‘hide’ themselves, allowing the body’s immune cells to attack and destroy tumors.

Natural Killer Cell Attacking Cancer Cell
The work looked at patients treated with immune checkpoint inhibitors, a therapy that disrupts the ability of cancer cells to “hide” themselves, allowing the body’s immune cells to attack and destroy tumors. (Pictured is a Natural Killer cell (red) attacking a cancer cell (blue) Credit: Dan Davis)

The researchers looked at whether patients had been given broad-spectrum antibiotics for up to 30 days prior to starting their immunotherapy treatment, or whether they had received antibiotics during their therapy — with respiratory infections being the most common cause for antibiotic prescriptions.

A total of 26 patients received antibiotics before and 68 received them during their immunotherapy, and the median overall survival after therapy was 14.6 months.

However, analysis found that patients who had previously taken antibiotics had a median overall survival of just two months, compared with 26 months for those who had not taken antibiotics prior to treatment. A similar effect was observed in all cancer types.

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Patients who had previously taken antibiotics were likely to respond less well to immunotherapy, with their primary disease nearly twice as likely to progress. The study also showed that the effect was independent of the antibiotic class used – which for this group of patients included beta-lactams, quinolones, macrolides, sulfonamides, tetracyclines, aminoglycosides and nitroimidazole.

CRITICAL TIMING

According to the researchers, more work is urgently needed to understand the mechanism behind the reduced response and decline in overall survival.

But they believe that broad-spectrum antibiotics before immunotherapy disrupt the balance of microbes in the gut — collectively called the microbiome — reducing the diversity of insects present and potentially impacting the body’s immune response.

“We know that giving antibiotics to patients affects their microbiome and increasing evidence shows it affects treatment outcomes,” Dr Pinato added.

Rod-shaped E.coli bacteria
Researchers believe broad-spectrum antibiotics before cancer immunotherapy upset the balance of microbes in the gut — collectively called the microbiome — reducing the diversity of insects present and potentially impacting the body’s immune response. Pictured are rod-shaped E.coli bacteria, which are part of the gut microbiome.
Credit: NIAID/NIH

“It’s important that patients who need antibiotics to treat bacterial infections get the drugs they need,” he explained. “But these findings push for more care in the decision-making process for some patients.

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It raises questions about whether we need a higher threshold for prescribing antibiotics to cancer patients because of immunotherapy.”

The team highlights some limitations of the findings, including the small number of patients, and a lack of direct observations of changes in the gut microbiome. They also add that it is not possible to fully account for the impact that other health problems the patients may have had (comorbidities) on their survival. However, they explain that they remain confident in the link and the need for further studies to expand on these findings.

The researchers now aim to conduct further studies to see what impact, if any, prior antibiotic use has on the microbiome of patients with a follow-up observational clinical trial funded by the NIHR Imperial Biomedical Research Center. They add that future studies could examine whether rebalancing or increasing the microbiome could improve patient outcomes.

The work was supported by Imperial College Healthcare NHS Trust Tissue Bank, and in part by the National Institutes for Health Research and the Wellcome Trust.

‘Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer’ by David Pinato et al. was published in JAMA Oncology. DOI: 10.1001/jamaoncol.2019.2785

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The post Antibiotics lower survival rates in cancer patients receiving immunotherapy | immuno Imperial news appeared first on Notesradar.

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