Do Corticosteroids Diminish Immune Checkpoint Blockade Efficacy?
It is possible that treatment with corticosteroids immediately before the initiation of PD-1/PD-L1 blockade could affect efficacy, said investigators.
Nivolumab and pembrolizumab programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibition (ICI) has changed lung cancer management in recent years, offering dramatic responses for a minority of patients. Unfortunately, most lung cancer responses to ICI are not deep or long-lived. That is partly because tumors evolve other molecular mechanisms of immune evasion. But recent research suggests another possible culprit: patients' baseline immunosuppressive steroid therapy could reduce the efficacy of ICI immunotherapy and patient survival time.
But, because patients on steroid therapy tend to be excluded from ICI clinical cancer trials, only nonrandomized, retrospective real-world data has been analyzed, making it unclear whether the correlation between steroid use and ICI outcomes could actually be causal.
Patients who took corticosteroids when they began administration of single-agent programmed PD-1/PD-L1 ICI therapy for non-small cell lung cancer (NSCLC) experienced lower overall response rates, worse progression-free survival (PFS), and poorer overall survival (OS), according to retrospective reviews of patient records at 2 leading cancer centers.1
The correlation remained statistically significant even in multivariate analyses that accounted for brain metastases and other potentially confounding variables, reported study coauthors from the Memorial Sloan Kettering Cancer Center, New York, New York and the Institut Gustave Roussy, Villejuif, France.1
“Prudent use of steroids at the time of initiating PD-1/PD-L1 blockade is recommended,” wrote lead study author Kathryn Cecilia Arbour, MD, from the Memorial Sloan Kettering Cancer Center.
“Corticosteroids, specifically systemic adrenal glucocorticoids, play a critical physiologic role in feedback inhibition of inflammatory responses and immune system homeostasis and have long been used for their immunosuppressive properties,” the authors noted.1
Nonsteroid alternatives for managing cancer symptoms should be considered if a patient might be administered PD-1/PD-L1–targeting immunotherapy, Dr Arbour said.
But patients should not forego “medically necessary” steroid therapy, such as those used for brain metastases, she cautioned. The central nervous system is 1 of the most common metastatic sites of NSCLC.2 Nearly a third (30%) of patients with NSCLC experience brain metastasis and half already have a metastatic brain tumor at the time of diagnosis of a primary lung cancer.