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Originally published September 22, 2025
Last updated September 23, 2025
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Corticosteroids are commonly used to manage lung cancer symptoms, yet they might be hindering the efficacy of certain immunotherapies, according to a new study led by Keck Medicine of USC researchers. Published in Cancer Research Communications, the study found that when non-small cell lung cancer patients were administered steroids before immune checkpoint inhibitor (ICI) immunotherapy, their tumors grew more quickly than those of patients who weren’t on steroids when treated with ICI immunotherapy. It also found that the patients didn’t live as long.
“Steroids were the biggest predictor of why certain immunotherapies may not be effective, even when considering multiple other factors such as stage and progression of the disease,” according to Fumito Ito, MD, PhD, lead study author and a medical oncologist and immunologist with the USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC. Other study authors included USC Norris medical oncologists Jorge Nieva, MD, and Robert Hsu, MD.
Ahead, Dr. Hsu discusses implications of this study and how these findings might inform future treatment protocols or dosage guidelines for lung cancer patients.
Dr. Hsu: In the study, we defined a high dose of corticosteroids as between 30 to 100 milligrams of prednisone daily, and a medium dose was between 7.5 and 30 milligrams daily.
The study showed that a high dose of prednisone was associated with markedly worse progression-free survival and overall survival compared to no steroid use. It also should be noted that no significant difference was observed between a medium dose and no steroids in both progression-free and overall survival. This means we saw a survival difference — this efficacy difference — with high-dose steroids, but we didn’t see it with medium-dose steroids and presumably wouldn’t see it with low-dose steroids.
Dr. Hsu: Yes, the outcomes did differ. In this study, there were 21 patients (8%) who were already on steroids at the start of immunotherapy. There were also patients who had been off steroids for at least one month prior to starting immunotherapy were not counted among the baseline steroid patients, and these patients had better outcomes.
Dr. Hsu: It depends on why the patients are getting steroids in the first place. Deciding on a treatment strategy requires a multidisciplinary discussion weighing the benefits of steroids use versus the benefits of immunotherapy for each patient and figuring out a path forward.
For instance, the most common reason lung cancer patients take steroids is because many of these patients, especially those with metastatic stage IV lung cancer, have cancer that has spread to the brain. These patients may have edema around their brain mass, and doctors will prescribe steroids to help blunt the inflammation around the site. In this case, expediting treatment for the brain metastasis might make it possible for a patient to eventually get off steroids. It could take the form of a collaboration between radiation oncology and neurosurgery by either getting the mass resected by neurosurgery or through radiation therapy.
But we do also have patients who are receiving steroids for other indications. For example, patients who have rheumatoid arthritis or other autoimmune disorders might be taking steroids to treat their disease. For these patients, you need to weigh the benefits of steroids and immunotherapy in the context of their condition.
Dr. Hsu: Our multivariate analysis included different variables: histology, whether patients got prior lung surgery, tobacco use, steroid use, race, ethnicity and cancer stage. At the Keck Medicine study site, we showed that race and ethnicity were not statistically significant but that smoking status was statistically significant. People who had never smoked did better than people who had smoked, with a hazard ratio of 0.63. We did not find statistically significant differences in histology between adenocarcinoma and squamous cell carcinoma. There were significant differences observed in steroid use, as per our main finding. And cancer stage had a major impact on mortality.
Dr. Hsu: Another basic science element we looked at was circulating CX3CR1+ CD8+ T cells in the peripheral blood, which are involved in T cell differentiation. We know that ICI anti-PD-1 immunotherapy really targets the signaling of T cells. Our study showed that these CX3CR1+ CD8+ T cells were substantially lower in patients on steroids. Another study in mice also confirmed this finding, showing that concurrent steroid use did significantly decrease the anti-tumor efficacy and attenuated the increase of circulating CX3CR1+ CD8+ T cells.
We talk a lot about patient outcomes from our study and other retrospective studies like it, but what is also important is these preclinical models that really give substantive evidence behind what we’re seeing from our retrospective clinical data.
Dr. Hsu: Some researchers are already aware of this phenomenon and are already taking it into consideration when designing exclusion criteria for clinical trial protocols. When you look at the inclusion and exclusion criteria for patients for clinical trials, especially ones that include use of immunotherapy, they often require patients to be on a low-dose steroid regimen of 10 milligrams or less of prednisone as a baseline. So, clinical trial protocols have already changed.
I do, however, think these findings have more impact in a real-world setting. Sometimes, there is an urgency to start patients on immunotherapy treatment. But, if they’re already on steroids — especially high-dose steroids — we may need to consider whether it’s worthwhile to start these patients on a high dose of immunotherapy. This study shows that it might be better to wait until the patient is weaned off their high dose of steroids before starting immunotherapy.
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