Real-world outcomes in older adults treated with immunotherapy: A United Kingdom multicenter series of 2,049 patients

Abstract

Background: Immune checkpoint inhibitor (ICI) therapy is now commonly used in a range of tumours and settings. Most data relating to outcomes and rates of immune-related adverse events (irAE) is derived from clinical trial or registry populations and small case series. Limited data exist for patients aged > 75 years. Here we present a multi-centre, real-world analysis of the outcomes and incidence of irAEs in older adults managed within a single comprehensive public health service. We also compare these outcomes to younger patients in the same cohort. Methods: A retrospective analysis of 2049 patients treated with ICIs was undertaken across 12 centres. All patients were managed within the UK National Health Service outside of a trial setting between June 2016 and September 2018. Patients received either ICI monotherapy (MT) or duel combination ICI therapy (CT) for malignant melanoma (MM), non-small cell lung cancer (NSCLC) or renal cell cancer (RCC). Data were collected using a standardised, collection tool. IrAEs ≥ grade 2 or all-grade endocrinopathies were recorded as per the Common Terminology Criteria for Adverse Events (V5) (CTCAE). Statistical analyses were performed using T-tests, Mann-Whitney and Chi-squared. Kaplan-Meier analysis and log-rank test were used for overall survival (OS) analysis. Results: 409 (20%) of patients were aged > 75 years(a), 1413 (69%) aged 50-75(b) and 227 (11.1%) aged < 50(c). There was no difference in sex, ethnicity or PD-L1 status (in the NSCLC cohort) between groups. Older patients were less likely to receive combination therapy (3%(a) v 13%(b) v 34%(c), p < 0.001). There was no difference in median OS across age groups in the cohort as a whole (p = 0.822) or for the individual tumour groups when treated with single agent ICI. Across the total cohort patients aged > 75 had no increased risk of any irAE (35%(a) v 33%(b) v 41%(c),p = 0.074). However there was an increase in irAEs in older patients treated with MT (36%(a) v 26(b) v 25%(c), p = 0.011) However there was no difference in the > 75s with regard to severe (G3/4) toxicity, toxicity type, admission or discontinuation due to toxicity in the aPD-1 group. In the overall cohort younger patients were more likely to develop irAEs and be admitted. Conclusions: Patients aged > 75 years treated with anti-PD1 therapy in the standard of care setting derive similar survival benefit to younger patients. There was no increase in ≥G3 toxicity. Our data support the safety of single agent aPD-1 ICI therapy in older adults and provide reassurance relating to the impact of toxicity.