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Age and Frailty Should Be Considered Independently When Evaluating Potential Risk for Side Effects Among Older Adults Treated with ICIs

Findings from a population-level retrospective cohort study
27 Jun 2022
Cancer Immunology and Immunotherapy;  Cancer in Special Situations / Population

Dr. Lawson Eng of the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre in Toronto, Canada and colleagues performed a population-level retrospective cohort study to evaluate the impact of age and frailty among older adults on use of acute care and immune-related adverse events (irAE) associated hospitalisations. Among older adults treated with immune checkpoint inhibitors (ICIs), age was not associated with use of acute care, but may be associated with reduced risk of experiencing an irAE associated hospitalisation. In contrast, frailty was associated with risk of use of acute care, but was not associated with risk of irAE associated hospitalisation. The study findings were presented at ASCO 2022 Annual Meeting in the oral abstract session on symptoms and survivorship.

The authors reported in the study background that ICIs are commonly used for treatment of various solid tumours. However, older adults are poorly represented in clinical studies that evaluated ICIs, especially those who are very old or frail. Although ICIs are better tolerated than chemotherapy, some patients develop irAEs that may require hospitalisation.

The study team used data linked across databases to identify a cohort of patients with cancer who are older than 65 years and received ICIs from June 2012 to October 2018 in Ontario, Canada. They obtained data on socio-demographic and clinical covariates, and use of acute care which was defined as an emergency visit or hospitalisation from initiation to 120 days after the last ICI dose. Hospitalisations were classified as irAE associated based on ICD-10 codes. Frailty was assessed using the McIsaac Frailty Index. Multivariable competing risk analyses with Fine Gray subdistribution hazards evaluated the impact of age and frailty on both, use of acute care and irAE associated hospitalisations adjusted for sex, rurality, BMI, autoimmune history, hospitalisation within 60 days prior to starting ICI and comorbidity score.

Among 2737 patients whose median age was 73 years, 18% were older than 80 years and 50% were between 70 and 79 years old. A total, 43% of patients were treated with nivolumab, 41% with pembrolizumab and 13% with ipilimumab. Majority of patients (53%) had lung cancer, following by melanoma (34%). Among patients, 70% were robust, 26% pre-frail and 4% frail. Most patients (72%) had an acute care episode, while 8% had irAE associated hospitalisation.

Older age was associated with reduced risk of being hospitalised due to irAE when measured as a continuous variable (adjusted hazard ratio [aHR] 0.97 per year, 0.95-0.99; p = 0.01). Those older than 80 years were also less likely to be hospitalised due to irAE; when compared age 70-79 years versus 65-69 years resulted in aHR 0.92 (0.66-1.27; p = 0.61), and comparison of age above 80 years versus 65-69 years resulted in aHR 0.63 (0.39-1.01; p = 0.05). Age was not associated with use of acute care as a continuous or categorical variable.

Increasing frailty was associated with increased risk of use of acute care during ICI treatment; when compared pre-frail versus robust patients aHR was 1.20 (1.07-1.36; p = 0.003), and when compared frail versus robust patients aHR was 1.45 (1.12-1.86; p = 0.004), but it was not associated with irAE hospitalisations.

When evaluating both age and frailty in the same model, the identified associations remained significant. The authors concluded that age and frailty may need to be considered independently when evaluating their use as potential factors influencing risk of toxicity among older adults receiving ICIs.

Research funding was reported from Conquer Cancer Foundation of the American Society of Clinical Oncology.

Reference

Eng L, Sutradhar R, Kaliwal Y, et al. Impact of age and frailty on acute care use during immune checkpoint inhibitor (ICI) treatment: A population-based study. J Clin Oncol 2022; 40 (suppl 16; abstr 12002). DOI: 10.1200/JCO.2022.40.16_suppl.12002

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