Impact of systemic corticosteroids for cutaneous immune-related adverse events on survival outcomes in patients with advanced cancer: A retrospective cohort study.
Authors: Yoon Jaewon , Thompson Leah L. , Krasnow Nira A. , Chang Michael , Li Edward , McMahon Devon , Polyakov Nicole , Molina Gabriel E. , Said Jordan , Huang Kevin , Kuchroo Juhi , Hinton Andrea , Reynolds Kerry Lynn , Chen Steven T 
Published: June 2021

e14523

Background: Cutaneous immune-related adverse events (cirAE) may disrupt immune-checkpoint inhibitor (ICI) therapy. Current guidelines recommend systemic corticosteroids (SCS) for moderate to severe cirAE, but SCS-associated complications and their impact on survival remain poorly understood. We therefore investigated the impact of SCS exposures on infectious complications and survival outcomes among patients with cirAE. Methods: We retrospectively reviewed the medical records of patients who initiated anti-programmed death-1/ligand-1 (PD-1/PDL-1) and/or anti-cytotoxic-T-lymphocyte-4 (CTLA-4) ICI therapy between 1/1/16-3/8/19 with confirmed cirAE, obtaining oncologic history, clinical features, SCS exposures, infection rates, and survival outcomes. SCS exposures were categorized by indication (cirAE, other immune-related adverse event, other medical reason) and dosage in prednisone equivalents (low, ≤7.5mg/day for ≥2 months; moderate, > 7.5mg/day for ≥2 months; high, ≥1mg/kg/day for ≥1 week). Infection rates were compared among patients treated with SCS for initial cirAE and those with no SCS exposures for any indication. Cox proportional hazards (CPH) models adjusted for age, sex, and covariates with P <0.05 were used to assess relationships between SCS for first cirAE episode, progression-free survival (PFS) and overall survival (OS). Results: 358 patients developed cirAE (median age 64 years, 40.5% female, 41.9% melanoma). 50 (14.0%) patients received SCS for initial cirAE, 192 (53.6%) received SCS for another indication, and 116 (32.4%) had no SCS exposures. Patients who received SCS for initial cirAE had higher median rash severity (Common Terminology Criteria for Adverse Events grade 3 vs. 1, P< 0.001) and were more likely to be hospitalized for cirAE management (20.0% vs. 1.9%, P< 0.001) than those who did not receive SCS. SCS delivery for initial cirAE was predominantly at low doses (n = 42, 84.0%). Infection rates were higher in patients who received SCS for initial cirAE than those with no SCS exposures for any indication (34.0% vs. 19.8%). Most infections in both groups required systemic therapy (88.2% vs. 95.7%). In multivariate models adjusted for age, sex, and SCS exposures by indication and dosage, patients who received SCS for initial cirAE and those who did not had similar PFS (HR 0.7, CI 0.4-1.3, P= 0.287) and OS (HR 3.0, CI 0.3-35.3, P =0.380). Conclusions: We observed higher rates of infection than previously reported among both patients who did and did not receive SCS for initial cirAE. Despite the theoretical risk of SCS impeding the anti-tumor response, we found no relationship between SCS for initial cirAE and PFS/OS. Collectively, these findings suggest that with appropriate management, low-dose SCS may be safely administered for cirAE without significant impact on survival outcomes.