The influence of sex on the impact of age and frailty on acute care use among older adults receiving immune checkpoint inhibitor (ICI) treatment: A population-based study.
Authors: Faour Elizabeth , Sutradhar Rinku , Kaliwal Yosuf , Niu Yue , Liu Ning , Powis Melanie Lynn , Liu Geoffrey , Peppercorn Jeffrey M. , Krzyzanowska Monika K. , Alibhai Shabbir M.H. , Eng Lawson 
Published: June 2023

12053

Background: ICIs are commonly used across solid tumors and although better tolerated than chemotherapy, patients may develop immune related adverse events (irAEs) requiring hospitalization. Older adults were poorly represented in trials evaluating ICIs. We previously demonstrated that among older adults receiving ICIs, increasing age was associated with reduced risk of irAE hospitalizations, while frailty was associated with increased acute care use (ASCO 2022). However, sex may impact irAE rates. Here, we evaluated sex-specific differences based on age and frailty, on acute care use and irAEs among older adults receiving ICIs. Methods: We performed a retrospective, population-based study of a cohort of patients with cancer, age ≥ 65, receiving ICIs between June 2012 and October 2018 in Ontario, Canada using administrative data. Databases were deterministically linked to obtain socio-demographic and clinical covariates, and acute care outcomes. Acute care use was defined as emergency department visits or hospitalizations from the start of ICIs to 120 days following last dose; irAE specific hospitalizations were identified using ICD-10 codes. Frailty was assessed using the McIsaac Frailty Index. Using death as the competing risk, multivariable competing risk analyses with Fine Gray sub-distribution hazards evaluated the effect of age and frailty on both acute care use and irAE hospitalizations, adjusted for body mass index (BMI), history of autoimmune condition, comorbidity score, rurality, and hospitalization within 60 days prior to starting ICI, stratified by sex. Results: 2737 patients were identified; 60% male. Median age 73 (IQR 69-78); 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab; 53% had lung cancer, 34% melanoma. 70% were robust (R), 26% pre-frail (PF) and 4% frail (F). 72% of patients had an acute care episode and 8% had an irAE hospitalization, which did not differ by sex (72%/8% male; 71%/8% female). Increasing frailty was associated with greater acute care use in males (PF vs R aHR 1.20 [95% CI 1.02-1.40] p = 0.03, F vs R aHR 1.42 [1.05-1.91] p = 0.02) and females (PF vs R aHR 1.24 [1.03-1.49] p = 0.02, F vs R aHR 1.55 [0.99-2.40] p = 0.05) but was not associated with irAE hospitalization in either sex. Using age as a continuous variable, increasing age was associated with reduced irAE hospitalizations in males (aHR 0.97 per year [0.94-0.99] p = 0.04), but not in females (p = 0.18); no significant associations were identified modelling age as a categorical variable. Conclusions: Among older adults receiving ICIs, increasing age was associated with reduced rates of irAE related hospitalization in males but not in females, while increasing frailty was associated with increased acute care use among both sexes. Sex should be taken into consideration when evaluating potential toxicity among older adults receiving ICIs.