Corticosteroids, which are commonly prescribed to alleviate cancer-related symptoms in patients with non–small cell lung cancer (NSCLC) treated with immunotherapy, may be the reason certain immunotherapies fail in treating the disease, according to new research published by Polyakov et al in Cancer Research Communications.
The study results showed that high doses of steroids, when given before and/or during immune checkpoint inhibitor therapy, caused patients’ tumors to shrink less than those of patients not on steroids. Those patients also did not 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,” said Keck Medicine of USC oncologist and immunologist Fumito Ito, MD, PhD, lead author of the research.
Additionally, researchers believe they have found the mechanism behind why steroids and some immunotherapies may not mix.
“Our findings reveal that steroids stop the body’s natural cancer-fighting cells, T cells, from maturing. This makes them unable to attack the cancer as vigorously as they usually would, leading to worse outcomes for patients,” explained Dr. Ito, who is also a member and co-leader of the translational and clinical sciences research program at USC Norris Comprehensive Cancer Center. “While other research has indicated steroids may negatively impact immunotherapy’s efficacy, we are one of the first [groups] to pinpoint a probable cause and effect.”
Dr. Ito and his colleagues also discovered that steroids blocked circulating biomarkers in the body. “Without the presence of circulating biomarkers to inform our decisions, oncologists cannot treat the cancer as effectively and patients may miss out on the best treatment for their cancer,” he noted.
The study examined the effect of steroids on immune checkpoint inhibitors, which are often used to treat NSCLC. Steroids are often prescribed to alleviate symptoms of the cancer or treatments given for a variety of reasons, such as fatigue and vomiting, or more serious side effects like brain swelling and lung inflammation. Steroids suppress the immune system, which reduces the inflammation that can cause these conditions.
Study Methodology
The researchers retrospectively studied the medical records of 277 patients with stage II to IV NSCLC who were treated with immune checkpoint inhibitors alone or in combination with other therapies. They compared outcomes (tumor shrinkage and survival rate) between patients who were prescribed steroids and those who were not at three centers. They analyzed up to 8 years of data to determine that steroids were the sole factor impeding the effectiveness of the immunotherapy.
They also determined that the T cells of significant numbers of patients on steroids were not fully matured and launched a preclinical study using mice to observe the effects of steroids on immune checkpoint inhibitor therapy in real time. This mouse model study led to the discovery that steroids given before or during immunotherapy inhibit T cells from fully maturing.
The Future of Steroid Use in NSCLC
While this new research indicates steroids can interfere with immune checkpoint inhibitor efficacy, the authors acknowledged that for some patients with NSCLC, steroids may be necessary to manage their cancer-related symptoms.
“We know that steroids will continue to play an important role in lung cancer care, but it is important to understand their potential limitations,” said Dr. Ito. “Each patient should talk to their oncologist to make sure they have the best possible care plan tailored to their specific needs.”
The investigators hope this research will lead to more studies examining the effect of steroids on immunotherapy, so oncologists can make fully informed decisions that will best benefit their patients.
Disclosures: The study was supported with grants from the National Cancer Institute as well as the Department of Defense Lung Cancer Research Program and the Uehara Memorial Foundation. For full disclosures of the study authors, visit aacrjournals.org/cancerrescommun.
