Regimen specific effects of baseline antibiotics and proton pump inhibitors in cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) containing versus non-CTLA-4 immunotherapy for lung cancer: A post hoc analysis of POSEIDON and CASPIAN trials

Each year, about 2.2 million people around the world are diagnosed with lung cancer. Lung cancer is the leading cause of cancer-related death for both men and women, responsible for around one in five cancer deaths. Most people with lung cancer (about 80–85%) have a type called non-small cell lung cancer, while a smaller group has small cell lung cancer. Small cell lung cancer (SCLC) is generally considered worse than non-small cell lung cancer (NSCLC) because it is much more aggressive, grows rapidly, and often spreads to other body parts before symptoms appear. While SCLC responds well to initial treatment, it frequently recurs, leading to a poorer overall prognosis. Despite advances in treatment, many patients still have limited survival, so improving how treatments work remains very important.

In recent years, a type of treatment called immune checkpoint inhibitor therapy has become a key part of lung cancer care. These treatments help the body’s immune system recognize and attack cancer cells. However, research has shown that bacteria living in the gut (often called the “gut microbiome”) can affect how well these immune treatments work. Some commonly used medicines, such as antibiotics (used to treat infections) and proton pump inhibitors (medicines that reduce stomach acid), can disturb these gut bacteria. Previous studies suggest that patients taking these medicines may not benefit as much from some immune therapies, but it is not yet clear whether this effect applies to all types of immune treatments.

Some immune treatments work by blocking a target called cytotoxic T-lymphocyte–associated protein 4, which plays an important role in activating immune cells. There is evidence that this type of treatment may be especially sensitive to changes in gut bacteria. Because of this, we will investigate whether antibiotics and proton pump inhibitors have a stronger negative effect in treatment plans that include this immune target compared with those that do not.

We will conduct this research by analyzing data that have already been collected from two large clinical trials involving people with lung cancer. These trials compared standard chemotherapy alone with chemotherapy combined with different immune treatments. Using this existing information allows us to fairly compare different treatment groups and understand how other medications taken at the start of treatment may influence outcomes.

In this study, we will examine whether patients who used antibiotics or proton pump inhibitors before starting cancer treatment lived shorter or had faster cancer growth compared with those who did not use these medicines We will use established statistical methods to compare patient outcomes across different treatment groups.

This research is necessary because it may help doctors better understand how everyday medications interact with cancer treatments. Our findings could guide future treatment decisions and help improve outcomes for people with lung cancer by identifying which combinations of medicines work best together.