Immune Checkpoint Inhibitors for Patients Aged ≥ 75 Years with Advanced Cancer in First- and Second-Line Settings: A Meta-Analysis

Background The impact of aging on the effectiveness of immune checkpoint inhibitors (ICIs) remains controversial, and little is known on the subject in adults aged ≥ 75 years. Objective The objective of this comprehensive meta-analysis was to assess the efficacy of ICIs in patients aged ≥ 75 years. Methods We performed a meta-analysis of published randomized controlled trials concerning ICIs (as monotherapy or in combination) versus standard therapy in patients with advanced solid tumors between January 2010 and January 2020. We compared overall survival between older (aged ≥ 75 years) and younger (< 75 years) patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. The secondary endpoint focused on the impact of the use of ICIs in first- and second-line settings. Results In total, 15 phase III studies evaluating anti-programmed cell death 1 (anti-PD-1) (nivolumab or pembrolizumab), anti-programmed cell death ligand 1 (anti-PD-L1) (atezolizumab or avelumab), or anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) (ipilimumab) therapies were included. Enrolled patients had non-small-cell lung cancer, renal cell carcinoma, melanoma, head and neck squamous cell carcinoma, or gastric cancer. Eight studies assessed treatment in the first-line setting and seven in the second-line setting. The median age was 64 years, with 906 patients aged ≥ 75 years (552 in first line, 354 in second line) and 8741 were aged < 75 years (4992 in first line, 3749 in second line). In the first-line setting, HRs for death were 0.78 (95% CI 0.61–0.99) in patients aged ≥ 75 years versus 0.84 (95% CI 0.71–1.00) in those aged < 75 years. In the second-line setting, HRs for death were 1.02 (95% CI 0.77–1.36) in patients aged ≥ 75 years versus 0.68 (95% CI 0.61–0.75) in those aged < 75 years, with a statistically significant difference observed between subgroups ( p = 0.009 for interaction). Conclusions ICIs appear to be effective in patients aged ≥ 75 years. However, the survival benefit is mainly observed in first-line treatment and remains unclear in the second-line setting.