Is Timing of Steroid Exposure Prior to Immune Checkpoint Inhibitor Initiation Associated with Treatment Outcomes in Melanoma? A Population-Based Study

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) have revolutionized the cancer treatment landscape, yet the impact of the timing of the use of an immunosuppressive agent such as steroids on ICI outcomes is poorly described. Utilizing the SEER-Medicare-linked dataset, this study explored the relationship between timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. We found steroid use up to 3 months prior increased risk for mortality up to 6 months after ICI initiation. Furthermore, steroid use was a significant contributor to poorer outcomes from ICIs, which should be considered before prescribing ICIs. ABSTRACT: Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1–3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65–3.08; and HR: 1.51, 95% CI: 1.01–2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.