Baseline Steroid Use Linked to Poorer Outcomes in ICI-Treated Lung Cancer

Fumito Ito, M.D., Ph.D.

Baseline corticosteroid use was associated with worse outcomes and diminished biomarker reliability in patients with non–small cell lung cancer (NSCLC) treated with immunotherapy, according to a study published July 7 in Cancer Research Communications. The study was led by Fumito Ito, M.D., Ph.D., an oncologist and researcher at the University of Southern California.

NSCLC is the most common type of lung cancer, about 87% of all lung cancers, according to the American Cancer Society. The five-year survival rate for non–small cell lung cancer was about 32% for patients between 2015 and 2021.

Non–small cell lung cancer is often treated with immune checkpoint inhibitors (ICIs). These immunotherapies help patients live longer by boosting the immune response against cancer cells to help shrink tumors or slow their growth. Examples include anti–PD-1 drugs such as Keytruda (pembrolizumab) and Opdivo (nivolumab) and anti–PD-L1s such as Imfinzi (durvalumab) and Tecentriq (atezolizumab).

However, corticosteroids are frequently prescribed to manage lung cancer symptoms. Although steroid use for immune-related adverse events does not appear to compromise ICI efficacy, baseline steroid use — that is, prior to or at the start of treatment — has been linked to poorer outcomes, raising concerns about immunosuppressive effects.

The new study evaluated 277 patients treated with immune checkpoint inhibitors at Roswell Park Comprehensive Cancer Center or the University of Southern California. Just 8% were taking steroids at treatment initiation, but these patients experienced significantly lower response rates and shorter progression-free and overall survival. Multivariate analyses identified baseline steroid use as the strongest independent predictor of disease progression and mortality.

Patients who discontinued steroids before immune checkpoint inhibitor therapy had better outcomes than those who continued. “The mere use of steroids was a more influential prognostic factor than the presence of brain metastases,” the authors wrote in their paper. Moreover, the analysis revealed that higher doses of baseline steroids were associated with worse patient outcomes than lower doses.

Baseline steroid use also seemed to affect the usefulness of blood-based immune markers. For instance, patients taking steroids had lower levels of CX3CR1+ CD8+ T cells, which help signal how well the immune system is fighting the cancer.

To explore underlying mechanisms, the researchers also conducted a study using anti–PD-L1 therapy in tumor-bearing mice with and without steroid exposure. In mouse models, steroids blunted the therapeutic benefit of anti–PD-L1 therapy and limited T-cell development. Even when steroids were stopped before treatment, earlier use still appeared to make this marker less reliable.

Similarly, while a neutrophil-to-lymphocyte ratio (NLR) below 5 was associated with better prognosis overall, this relationship was not observed in patients taking steroids, further complicating interpretation of immune biomarkers.

Although the number of patients taking steroids was small and biomarker data were incomplete for some participants, the authors noted these limitations and emphasized that the findings still support efforts to reduce steroid use before starting immune checkpoint inhibitor treatment. They suggested that future studies should explore whether lowering or stopping steroids could lead to better clinical outcomes for patients.