Impact of Patient’s Age on Efficacy of Immune Checkpoint Inhibitors in Advanced Cancers: A Systematic Review and Meta-Analysis

Abstract

The effects of immunosenescence on the efficacy of immune checkpoint inhibitors (ICI) in advanced cancers are unclear. We aimed to assess the difference in efficacy of ICI in advanced cancers between age groups ≥75 versus (vs) < 75 years old and ≥ 65 vs <65 years old. We searched various biomedical databases for randomized trials (RCTs) comparing ICI with standard of care for treatment of advanced cancers that had available hazard ratios (HR) for overall survival (OS) according to the age groups (≥ 75 vs < 75 years old or ≥ 65 vs <65 years old). We calculated the pooled OS HR and its 95% confidence interval (CI) in the predefined age groups using a random-effects model and assessed the heterogeneity between the two estimates using an interaction test. Subgroup analyses include disease site, line of therapy, class of ICI and trial design. We found nine RCTs (5667 patients) for age groups ≥ 75 vs < 75 years old and 23 RCTs (13623 patients) for age groups ≥ 65 vs <65 years old. The difference in efficacy between ≥ 75 years old (HR 0.90 (95%CI 0.67-1.21)) and < 75 years old (HR 0.76 (95% CI 0.63-0.91)) was not significant (interaction p (IP) = 0.34). Subgroup analyses showed that there was a significant difference in efficacy between ≥75 years old (HR 1.19 (95%CI 0.85-1.68)) and < 75 years old (HR 0.73 (95% CI 0.63-0.84)) (IP = 0.01) in the second line setting. There was no difference in efficacy between age groups ≥ 65 (HR 0.77 (95% CI 0.70-0.86)) and <65 years old (HR 0.75 (95% CI 0.68-0.84)) (IP= 0.73). Subgroup analyses for age groups (≥65 vs <65 years old) recapitulated these findings. The efficacy of ICI in patients ≥ 75 years old in the second line setting is significantly lower compared to patients < 75 years old. Future studies should focus on improving the efficacy of immunotherapies in elderly patients.