Patients live longer if they do not take antibiotics in month before immunotherapy

Taking antibiotics in the month before starting immunotherapy dramatically reduces a cancer patient’s chances of survival, according to a small but groundbreaking study.

Scientists at Imperial College London believe antibiotics strip out helpful bacteria from the gut, which weakens the immune system. This appears to make it less likely that immunotherapy drugs will boost the body’s cancer-fighting capability.

In their study of nearly 200 cancer patients in two NHS hospitals, the researchers found that those who had taken broad-spectrum antibiotics for just a few days for common problems such as chest infections survived for a median of two months after immunotherapy, compared with 26 months for those who had not been on antibiotics.

The substantial difference in survival, and clear evidence from CT scans that tumours grow more rapidly in those who have taken antibiotics, has led the researchers to call for more work to be done urgently to guide doctors.

“Antibiotics clearly wipe out some of the gut microbiota,” said Dr David Pinato, from ICL’s department of surgery and cancer, who was one of the authors of the study published in the journal Jama Oncology. “If you have got a good microbiome, you are more likely to have educated your immune system to fight cancer better.”

The results were the same no matter which antibiotics people were on or the type of cancer they had. In lung cancer, where chest infections are more common, median survival was 2.5 months in those who had been on antibiotics before starting the immunotherapy drugs, known as checkpoint inhibitors, versus 26 months in those who had not. In melanoma it was 3.9 versus 14 months, and in other tumours five weeks versus 11 months.

The patients on antibiotics were not particularly ill. They were not on drips in hospital but tended to be taking a brief course of five to seven days as outpatients. Importantly, the outcomes and survival rates of patients who received antibiotics while they were on immunotherapy were not affected.

It is already well known that some people respond much better to immunotherapy than others. In about 20% the cancer disappears completely and there can be hopes of a cure, but others do not do well. Scientists and commercial companies are hunting for reasons, looking at the type of tumour and its molecular traits.

Pinato said the strong finding in their small observational study was unexpected. Others studies had suggested different factors that might reduce survival, “but this association seems to be pretty solid”, he said.

It will not be the only reason for poor immunotherapy outcomes, but the authors say it is imperative that more research is done to establish how much of a factor it is.

“It is important that patients who need antibiotics to treat bacterial infections receive the drugs they need,” said Pinato. “But these findings urge 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 health service is already under pressure to use antibiotics only when necessary, in order to conserve their power to kill dangerous strains of bacteria by avoiding resistance developing. “This probably adds a further layer of complexity to the idea of antibiotic stewardship,” said Pinato.

The findings also provoke questions as to whether strengthening the gut microbiome might help the immune system fight cancer, an issue the ICL team now hope to explore.