Corticosteroids at Time of PD-L1 Blockade May Reduce Efficacy in NSCLC

Taking corticosteroids at the time of treatment initiation with programmed cell death-1 or programmed death ligand 1 (PD-L1) inhibitors may lead to inferior outcomes in patients with non–small-cell lung cancer, according to a retrospective study published in the Journal of Clinical Oncology.

The current standard of care for patients with NSCLC includes treatment with PD-L1 inhibitors. Lead study author Kathryn C. Arbour, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, said controversy has surrounded the use of corticosteroids given their immunosuppressive properties. In particular, she said, clinicians are concerned that they may impact the efficacy of immune checkpoint inhibitors.

“Thus far, the impact has been unknown given that patients on baseline steroids were not included in the clinical trials of such agents. This analysis from two independent cancer centers demonstrates that lung cancer patients receiving baseline steroids treated with a single agent PD-1 or PD-L1 inhibitor had inferior outcomes compared with those patients not on baseline steroids,” Dr. Arbour told Cancer Network.

Researchers looked at patients who were PD-L1–naïve with advanced NSCLC at two institutions, Memorial Sloan Kettering Cancer Center and Gustave Roussy Cancer Center in France. They examined clinical and pharmacy records and performed multivariable analyses. The analysis revealed that 90 of 640 patients (14%) treated with single-agent PD-L1 blockade received ≥ 10 mg of prednisone equivalent daily at the start of the PD-L1 blockade. The most common indications for corticosteroids were dyspnea (33%), fatigue (21%), and brain metastases (19%), according to the authors.

At both institutions, baseline corticosteroids were associated with decreased overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) when given with PD-L1 blockade. After adjusting for smoking history, performance status, and history of brain metastases, the researchers found baseline corticosteroids remained significantly associated with decreased PFS (HR, 1.3) and OS (HR, 1.7).

“Although retrospective, the data suggest that steroids should be used with caution at treatment initiation and reserved only for medically necessary indications,” said Dr. Arbour. “Although we cannot fully differentiate the predictive versus prognostic effects of steroids, we believe that steroids should be used with caution at treatment initiation but still urge that medically necessary steroids should not be avoided.”

Arbour noted that this study included only patients receiving single agent PD-1 or PD-L1 inhibitors, and therefore it is unknown if baseline corticosteroids may similarly affect the outcomes of lung cancer patients treated with chemotherapy and immunotherapy in combination.

Ramaswamy Govindan, MD, Professor of Medical Oncology at Washington University School of Medicine and a Siteman Cancer Center research member in St. Louis, Missouri, said these findings may be clinically relevant if they are validated in follow-up studies. “This is an interesting study. Steroids are used commonly in patients with advanced lung cancer for a wide variety of reasons, for COPD and lung inflammation, prior to chemotherapy, to control nausea. If these findings are confirmed, they will have an impact in the clinic,” Govindan told Cancer Network.