Cancer Immunotherapies: Are They as Effective in the Elderly?
Kate Poropatich1, Joel Fontanarosa2, Sandeep Samant2
1Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
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.
Insights
Advanced age does not generally hinder immunotherapy safety or response in cancer patients. However, specific immune checkpoint inhibitors show drug-dependent differences in elderly individuals, requiring further research for optimized treatment.
Area of Science:
- Oncology
- Immunology
- Geriatrics
Background:
- Cancer incidence significantly increases in individuals over 65, a demographic often underrepresented in preclinical research.
- Immunotherapy is a growing first-line treatment for advanced cancers, but its efficacy and safety in older adults remain under investigation.
- Human ex vivo studies show age-related immune system changes, including increased regulatory immune cells and altered T cell ratios.
Purpose of the Study:
- To evaluate the impact of age on patient response and safety to cancer immunotherapy.
- To analyze clinical response data from phase II/III trials stratified by age groups (young vs. old).
Main Methods:
- Review and meta-analysis of clinical response data from 21 phase II/III immunotherapy trials.
- Age stratification into young and old subgroups for comparative analysis.
- Examination of safety profiles, overall survival, and progression-free survival.
Main Results:
- Immunotherapy, particularly immune checkpoint inhibitors, demonstrates a generally low toxicity profile and is well-tolerated in both young and elderly cancer patients.
- Contrary to expectations, advanced age does not appear to significantly hinder overall safety or clinical response to most immunotherapies.
- Drug-specific variations were observed in elderly patients regarding overall survival and progression-free survival compared to younger cohorts.
Conclusions:
- Cancer immunotherapy is largely safe and effective across age groups, including older adults.
- Further research is necessary to identify specific immune checkpoint inhibitors and patient subgroups within the elderly population who may benefit most.
- Optimizing immunotherapy for heterogeneous elderly cancer patients requires better stratification of responders and non-responders.
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