Investigating the impact of immune related adverse events, glucocorticoids use and immunotherapy interruption on long-term survival outcomes.

Abstract

e14551 Background: It remains unclear whether immune related adverse events (irAEs) and glucocorticoids use could impact long term-outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). Methods: All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective multicentric study. Objectives were to assess the impact of grade 3+ irAEs, glucocorticoids use and interruption of immunotherapy on progression free survival (PFS) and overall survival (OS). Data collection was performed retrospectively using a standardized data collection form. Adverse events were categorized as irAEs based on the judgement of the treating physicians, based on the common Terminology Criteria for Adverse Events, version 4.0. Only grade 3 and more irAEs were considered in this study. As irAEs might happen late during the follow-up and progression event or death might happen early, an immortal-time bias might occur as patients responding to ICI will receive the ICI and then be exposed to irAE for a longer period of time. The first occurrence of an irAE was then included in Cox models, as a time-varying covariate. Similar methods were used to evaluate the impact of glucocorticoids introduction or ICI interruption. Results: In this 828 patients’ cohort, 78 patients presented at least one grade 3+ irAE. The first occurrence of grade 3+ irAEs had no significant impact on PFS (HR 0,94; 95%CI 0.7-1.26; p = 0,70) or OS (HR 0.82; 95%CI 0.6-1,12; p = 0,21). 65% of patients with anti CTLA4 and 55% of patients with anti PD(L)1 requested glucocorticoids, which was associated with a significant shorter PFS (adjusted HR 3.0; 95%CI 1.6-5.4; p = 0.00040) and a trend toward shorter OS. Grade 3+ irAEs led to interruption of the ICI in 82 % of patients, which was associated with a significant shorter PFS (adjusted HR 3.5; 95%CI 1.7-6.0; p < 0.00043) and shorter OS (HR 4.5; 95%CI 1.7-12.1; p = 0.0027). The use of glucocorticoids was statistically associated with immunotherapy interruption. Conclusions: 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.