Impact of systemic corticosteroids on survival outcomes in patients with immune-checkpoint inhibitor enterocolitis.

Abstract

e15065 Background: Current guidelines for immune-checkpoint inhibitor enterocolitis (ICI-EC) recommend systemic corticosteroids (SCS) for moderate to severe cases, but whether these therapies have an impact on survival outcomes remains unclear. Prior work has been limited, considering only select cancer types, ICI regimens, and indications for immunosuppression. We therefore sought to examine the relationship between SCS for ICI-EC and survival outcomes, accounting for all other steroid exposures. Methods: We retrospectively reviewed the medical records of patients with biopsy-confirmed ICI-EC seen at our institution between August 2011 and April 2019, collecting patient demographics, cancer features, anti-neoplastic therapies, other immune-related adverse events (irAEs), SCS exposures, progression-free survival (PFS), and overall survival (OS). We further categorized SCS exposures by indication (ICI-EC, other irAE, other medical reason) and previously established dose thresholds (“high” ≥1mg/kg for ≥1 week; “moderate” ≥7.5mg for ≥2 months, or “none”). We assessed the relationship between SCS use for ICI-EC and PFS/OS using Cox proportional hazards models adjusted for age, sex, cancer type and stage, baseline brain metastases, functional status (Eastern Cooperative Oncology Group score), anti-neoplastic therapies, and other SCS exposures. Results: 90 patients (mean age 62.5 years, 37.8% female) had biopsy-confirmed ICI-EC, most commonly precipitated by CTLA-4 monotherapy (43.3%). Nearly all (80.0%) required SCS for their first episode of ICI-EC, with half (46.7%) requiring doses exceeding the highest threshold. Patients who received high-dose SCS for first ICI-EC episode had reduced PFS (HR = 2.50, p = 0.028) compared to those who did not receive SCS for this indication. OS was not affected by SCS therapy for ICI-EC at any dose. Conclusions: In cancer patients with biopsy-proven ICI-EC, receipt of high-dose SCS for first ICI-EC episode was associated with decreased PFS, but not OS. These findings suggest a nuanced and potentially dose-dependent relationship between SCS and survival outcomes meriting further investigation for a larger array of immunotoxicities.