Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

SIMPLE SUMMARY: Immunotherapy has modified our clinical practices for the treatment of various solid cancers. Many studies have been done but it remains unclear whether adverse events induced by immunotherapy and the corticoids used for their management could impact long-term outcomes in patients treated by immunotherapy. A data collection of 828 patients was made to assess the impact of adverse events, immunotherapy interruption and the use of corticoids in long-term outcomes. In this cohort, we did not find any association between adverse events and survival outcomes. However, corticoid use was associated with a significantly shorter time before disease progression. Immunotherapy interruption was associated with a significantly shorter time before progression and survival. The impact of severe adverse events related to immunotherapy reported in other studies might be explained by their management. The use of corticoids must be careful, and resuming immunotherapy after adverse events may be important for long-term prognosis and should be considered as often as possible. ABSTRACT: It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.