Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-analysis
Abstract
Background Immune checkpoint inhibitors (ICIs) rely on the presence of ongoing immune response to exert their antitumor effect. Little is known whether an age-related decline in immune function negatively influences antitumor response and in so doing diminishes the efficacy of ICIs in elderly subjects. We performed a meta-analysis to compare the efficacy of ICIs between younger and older patients.Patients and methods PubMed and the ASCO databases were searched up to September 2015. We included randomized controlled trials (RCTs) of ICIs (ipilimumab, tremelimumab, nivolumab and pembrolizumab) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.Results A total of 5265 patients from nine RCTs of ICI were included. When patients are dichotomized into younger and older groups with an age cut-off of 65-70 years, ICIs improved OS in both younger (HR, 0.75; 95% CI, 0.68-0.82) and older (HR, 0.73; 95% CI, 0.62-0.87) groups. An improvement in PFS was observed in younger (HR, 0.58; 95% CI, 0.40-0.84) and older (HR, 0.77; 95% CI, 0.58-1.01) patients. Subgroup analyses according to ICI and tumor type showed a consistent survival benefit in both younger and older groups except for the subgroup of older patients treated in 4 trials of anti-programmed cell death protein-1 (PD-1) monoclonal antibody (HR, 0.86; 95% CI, 0.41-1.83).Conclusions A benefit in OS with ICIs was significant in both younger and older patients with a cut-off age of 65-70 years.
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Anti-PD-1 drugs cause no increased toxicity in elderly patients.
“with no increased toxicity [155–158].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [158]
Anti-PD-1 drugs are effective for both young and elderly patients.
“A meta-analysis of randomized trials showed that although anti-PD-1 drugs are effective for both young and elderly patients, the risk of death among elderly patients is comparable or improved compared to that of patients subjected to control interventions, with no increased toxicity [155–158].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [158]
The risk of death among elderly patients receiving anti-PD-1 drugs is comparable or improved compared to control interventions.
“the risk of death among elderly patients is comparable or improved compared to that of patients subjected to control interventions, with no increased toxicity [155–158].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [158]
In a meta-analysis of randomized controlled trials of immune checkpoint inhibitors, response rates of young and old cancer patients were very similar, suggesting that aging does not influence the function of exhausted T cells.
“In a meta-analysis of randomized controlled trials of immune checkpoint inhibitors (ipilimumab, tremelimumab, nivolumab, and pembrolizumab), the response rates of young and old cancer patients were very similar, suggesting that aging does not influence the function of exhausted T cells”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Nishijima et al., 2016
A recent meta-analysis analyzed the contextual administration of anti-CTLA-4 (tremelimumab and ipilimumab) and anti-PD-1 (nivolumab and pembrolizumab) molecules in four settings: melanoma, prostate cancer, renal cell carcinoma, and NSCLC.
“However, a recent meta-analysis analyzed the contextual administration of anti-CTLA-4 (tremelimumab and ipilimumab) and anti-PD-1 (nivolumab and pembrolizumab) molecules in four different settings: melanoma, prostate cancer, renal cell carcinoma, and NSCLC.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [175]
The authors demonstrated a 37% reduction of the risk of death in favor of immune checkpoint inhibitors compared with the control arm.
“The authors demonstrated a 37% reduction of the risk of death in favor of immune checkpoint inhibitors compared with control arm (175).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [175]
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- Authors
- Nishijima, T. F., Muss, H. B., Shachar, S. S., & Moschos, S. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Nishijima, Tomohiro F.
- Venue
- Cancer Treatment Reviews
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 45
- Pages
- 30-37
- ISSN
- 0305-7372 (ISSN-L)
- OpenAlex
- W2288908606
- Cited by
- 293
- References
- 40
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 19 · 2023: 26 · 2022: 37 · 2021: 36 · 2020: 42 · 2019: 33 · 2018: 36 · 2017: 23 · 2016: 4
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Treatment Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- immune checkpoint inhibitors, elderly patients, age-related immune decline, ipilimumab, tremelimumab, nivolumab, pembrolizumab, PD-1 inhibitors, overall survival, progression-free survival, antitumor immunity, cancer immunotherapy
- MeSH terms
- Age Factors, Aging, Antibodies, Monoclonal, Antineoplastic Agents, Humans, Neoplasms, Randomized Controlled Trials as Topic, Treatment Outcome, Disease-Free Survival
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