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Can PPIs impact lung cancer treatment?


Jolyon Attwooll


26/11/2021 1:08:12 PM

New research suggests a common medication used by up to 30% of cancer patients may adversely affect immune therapy treatment.

PPI prescription
Up to 30% of cancer patients use PPIs, often for extended periods.

A new study has indicated that certain types of lung cancer treatment could be impaired if patients are also taking proton pump inhibitors (PPIs).
 
PPIs, used to treat heartburn and reflux since the 1990s, are prescribed widely to cancer patients.
 
Researchers at Flinders University carried out a secondary analysis of the results of Impower150, an international study involving 1202 patients with advanced lung cancer.
 
Their article, published in a recent edition of the British Journal of Cancer, includes the hypothesis that the use of PPIs could cause gut microbiota changes that affect the efficacy of atezolizumab, an immune checkpoint inhibitor (ICI) drug.
 
The lead author is Dr Ash Hopkins, who is leader of the Clinical Cancer Epidemiology Lab at Flinders University.
 
‘Stomach issues and reflux are common in cancer patients so the use of antacids and PPIs is common,’ Dr Hopkins said.
 
‘Of concern is that the medication is often overused, or used inappropriately, as it is seen to cause little harm; however, our research could indicate a need to change this approach.’
 
The researchers found an association between those using PPIs who were treated with atezolizumab and chemotherapy and worse survival rates. They found no link to worse survival rates in patients who received chemotherapy alone.
 
The authors suggest the analysis indicates PPIs usage could decrease the benefits of the immune therapy treatment.
 
‘ICI drugs help the immune system by switching on T-cells, allowing them to kill or control cancerous tumours, but the gut microbiota also plays an important role in regulating our body and its immune function,’ Dr Hopkins said.
 
‘When this gut microbiota is impacted it can stop the ability of ICIs to activate the immune system, meaning the drugs simply won’t work as well to fight off the cancer.’
 
The authors hope the study will prompt further investigation seeking more conclusive data for the heartburn drugs’ impact.
 
‘With up to 30% of cancer patients using PPIs, often for extended periods or seemingly from a perspective that there will be no harm, the present study exemplifies an urgent need to conclusively determine if PPIs influence ICI efficacy and for oncologists to consider whether a PPI is critically necessary for an individual,’ the article reads.
 
Associate Professor Joel Rhee, Chair of RACGP Specific Interests Cancer and Palliative Care, describes the study as interesting, but does not think it has immediate clinical implications for GPs.
 
However, he says it reinforces the need to be mindful when prescribing PPIs.
 
‘One of the [study’s] recommendations is that, unless a patient really requires proton pump inhibitors, then don’t give them,’ he told newsGP. ‘That’s definitely reasonable.
 
‘With proton pump inhibitors, there’s a recognition [they are] often overused. We’re not just talking about cancer patients, but we’re talking about patients in general.
 
‘Often they start it for a particular reason, and it is just continued even if that original reason has been resolved.
 
‘It’s important as GPs that we review patients’ medications regularly, particularly with proton pump inhibitors.
 
‘If there’s no good reason [for continuing it], then you can try reducing or stopping it, and that’s going to be good for patient care.’
 
However, he said if a patient is exhibiting strong reflux symptoms, then there would be a good case for prescription.
 
‘Obviously, medications when they’re used for good reasons can be highly beneficial for patients,’ he said. ‘We just need to make sure that’s the case.’
 
According to the Cancer Council, lung cancer causes more deaths than any other cancer in Australia. It accounts for almost 20% of mortalities from cancer in the country and makes up 9% of cancer diagnoses overall.
 
The Cancer Council estimates there will be around 13,810 cases of lung cancer diagnosed in the country this year.
 
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Dr Michael Lucas Bailey   30/11/2021 7:38:41 AM

Studies like this are an interesting data analysis but need to be considered very very critically. For example it needs to be noted that this is by definition an observational study rather than a randomised control trial. There is no comment on confounders. There is no assessment of indication - why were those patients prescribed PPIs? Is the PPI the problem or an indication of another primary issue such as obesity related relux, hiatus hernia, Barrett’s oesophagus, oesophageal dysmotility or something else. Is the underlying indication related to another risk factor also associated with the indication for the PPI - such obesity in the context of diabetes, cardiovascular disease.

Also it is noted this was a secondary data analysis so in addition to being observational this data wasn’t collected for this purpose. That adds complexities to the accuracy of the data’s collection and management.