Impact of Proton Pump Inhibitor Use on Outcomes with Atezolizumab-Based Therapy in Metastatic and Adjuvant Renal Cell Carcinoma: A pooled exploratory Analysis from IMmotion150, IMmotion151, and IMmotion010

Kidney cancer, also called renal cell carcinoma (RCC), affects thousands of people each year. When it spreads to other parts of the body (metastatic, mRCC), it becomes harder to treat. In recent years, new treatments called immunotherapies—medicines that help the body’s own immune system attack cancer—have improved outcomes for many patients. One important type of immunotherapy is immune checkpoint inhibitors (ICIs). These drugs block “brakes” on the immune system that cancer cells use to hide, allowing immune cells to better recognize and destroy tumors. ICIs are often used alone or together with medicines that block the tumor’s blood supply.

Although these approaches have helped many people live longer, they do not work for everyone, and we still do not fully understand why. In earlier-stage kidney cancer, where the tumor has been removed with surgery, the benefits of immunotherapy are also uncertain. One drug, pembrolizumab (an ICI), has shown clear benefit for patients at high risk of the cancer returning, but similar drugs have not always shown the same results. This inconsistency suggests that other factors may influence how well immunotherapy works.

One possible factor is the gut microbiome, which is the community of bacteria living in the digestive tract. These bacteria help regulate the immune system. Research suggests that changes in gut bacteria may affect how well ICIs work. This matters because many people with cancer take medicines called proton pump inhibitors (PPIs) to reduce stomach acid. PPIs can disrupt gut bacteria, and several studies have linked PPI use to worse outcomes in RCC patients treated with both immunotherapy and older targeted drugs.

We will study whether PPIs influence how well immunotherapy works in kidney cancer. To do this, we will analyze data from three large clinical studies: IMmotion150 and IMmotion151, which tested immunotherapy in metastatic RCC, and IMmotion010, which tested immunotherapy after surgery in earlier-stage disease. All three studies used an immunotherapy drug called atezolizumab, either alone or with bevacizumab, (a drug that inhibits blood vessel growth in tumors) and compared it to standard treatments.

We will examine whether taking a PPI shortly before or shortly after starting cancer treatment is linked to differences in survival. We will compare patients who received immunotherapy with those who received standard treatments, and we will consider other factors that might influence outcomes, such as overall health and use of other medications.

By understanding whether PPIs reduce the benefit of immunotherapy, we hope to provide practical guidance for doctors. If PPIs are shown to have a harmful effect, we will encourage more cautious use of these medicines in patients with kidney cancer who are receiving immunotherapy.