Cancer Immunotherapies: Are They as Effective in the Elderly?

Abstract

Almost two-thirds of all new cancer diagnoses are made in persons over the age of 65 years, yet it is unclear if age affects patient responsiveness to immunotherapy, which is increasingly becoming first-line therapy in advanced stages of different tumor types. Preclinical animal studies may be difficult to translate into humans since they frequently use young mice (2-3 months of age) equivalent to adolescent human subjects. Nevertheless, ex vivo studies from humans are concordant with mice tissue findings-older patients have an increased density of circulating regulatory immune cells and a decreased ratio of naïve-to-memory T cells. A review of different immunotherapy trials reveals that contrary to expectations, advanced age generally does not hinder safety and clinical response to different treatment modalities. A growing number of immune checkpoint inhibitor immunotherapy trials have been published with basic safety and clinical response data stratified by age. We present the clinical response data from 21 phase II/III clinical trials based on age stratification into young and old subgroups. Data from these trials indicate that these agents have an overall low toxicity profile and that they are similarly well-tolerated in young and old patient subgroups. However, drug-specific differences exist for immune checkpoint inhibition in elderly subjects when comparing overall survival and progression-free survival hazard ratios with those of young subjects. Additional work is needed to better stratify 'responders' and 'nonresponders' within the elderly age group in order to optimize immunotherapy use in a heterogeneous patient population.