Association of Systemic Steroid Treatment and Outcome in Patients Treated with Immune Checkpoint Inhibitors: A Real-World Analysis

Abstract

Background: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy. Methods: We retrospectively evaluated 146 patients with metastatic non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma (RCC) treated with ICIs. We assessed the progression-free survival (PFS) of patients treated with steroids due to an irAE compared to a no-steroid group. Results: The early treatment with steroid (within the first 30 days from the beginning of immunotherapy) was not related to a shorter PFS (p = 0.077). Interestingly, patients who were treated with steroids after 30 days from the start of immunotherapy had significantly longer PFS (p = 0.017). In a multivariate analysis, treatment with steroids after 30 days was an independent prognostic factor for PFS (HR: 0.59 [95% CI 0.36–0.97], p = 0.037). Conclusions: This retrospective study points out that early systemic steroids administration to manage irAEs might not have a detrimental effect on patient clinical outcome in NSCLC, melanoma and RCC patients.

Immune-Related Thyroiditis as a Predictor for Survival in Metastatic Renal Cell Carcinoma

“…Following the observed protective effect of irT on survival in the high-risk group patients, we studied the prevalence and effect on survival of additional immune-related adverse events (irAE) in the whole population and in the high-risk group. Having any non-thyroid irAE had a protective effect in the whole cohort as in previous reports [6,7,10], as did a history of treatment with high-dose steroids for irAE; this is in agreement with a recent report [29]. Other specific irAEs were not associated with survival in our cohort, possibly due to their low frequency.…”

The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy

“…One study of 156 patients examined OS in patients who received glucocorticoids within 30 days or after 30 days of initiation ICIs for irAEs. This study showed no association in glucocorticoid use and overall survival and a possible improved outcome for those who started steroids after 30 daysalthough this is prone to immortality bias (15). A separate retrospective study including 257 patients who received steroids for irAEs showed decreased overall survival if glucocorticoids were initiated within two months of ICI onset after adjusting for glucocorticoid indication including tumor site, brain metastases, and the type of irAEs (14).…”

“…Use of glucocorticoids to treat irAEs The associated effects of glucocorticoids on cancer outcomes when used for the treatment of irAEs is difficult to interpret. While glucocorticoids may mitigate the immune effects of ICIs, irAEs themselves may be a prognostic marker for enhanced tumor response to ICIs (15). Ideally, the comparison of outcomes between patients with the same irAEs treated with and without glucocorticoids in a clinical trial would provide more clarity but has obvious ethical considerations, as these agents are recommended as first-line treatment for irAE in clinical practice guidelines (3)(4)(5).…”

“…Overall, the current data suggests that the use of glucocorticoids for irAEs may not have a large deleterious effect on overall survival. However, one needs to consider that most patients with irAE receive glucocorticoids initially and that the development of irAE may be associated with better response to ICI, as it may indicate a more robust immune response ( 15 ). Some data suggests that early use of glucocorticoids (within 60 days of ICIs) may be associated with worse cancer outcomes, but further studies are needed to validate this finding.…”

Mechanisms of dermatological toxicities to immune checkpoint inhibitor cancer therapies

“…However, mixed evidence exists as to whether the use of systemic corticosteroids decreases the effectiveness of ICIs. [84][85][86][87][88] One of the most salient features of cutaneous irAEs is their significant impact on prognosis. 89 MAV, whether arising spontaneously or as a result of ICIs, has been well established as a predictor of favourable outcomes and good prognoses.…”