Influence of age on the efficacy of immunochemotherapy in non-small cell lung cancer.

Objective: There is uncertainty about how age affects the efficacy of immunotherapy due to the natural process of immunosenescence. The aim of this systematic review and meta-analysis is to assess whether age over 65 years affects the efficacy, in terms of overall survival, of immunotherapy treatments in combination with chemotherapy or double immunotherapy, used in first-line metastatic non-small cell lung cancer without molecular alterations.

Methods: A systematic review and meta-analysis were performed. A systematic search of PubMed and Cochrane Library until April 30, 2024 was conducted to identify randomized clinical trials comparing an experimental treatment with immune checkpoint inhibitors plus chemotherapy versus a platinum-based chemotherapy doublet in patients with locally advanced or metastatic non-small cell lung cancer, without molecular mutations and with any level of programmed death ligand 1 expression. The primary endpoint was the difference in efficacy between those older and younger than 65 years, measured in terms of difference in overall survival hazard ratio. We calculated the hazard ratio for overall survival with its 95% confidence interval in both age groups and assessed heterogeneity using an interaction test.

Results: A total of 1,505 publications were identified, of which 7 clinical trials were included. In addition, the European public report evaluating pembrolizumab in combination with platinum and nab-paclitaxel was incorporated. In total, the analysis included 5,572 patients: 2,893 under 65 years of age and 2,679 aged 65 years or older. The pooled Hazard Ratio for overall survival for patients in the first group was 0.68 (95% CI: 0.62-0.74), and for the second 0.77 (95% CI: 0.70-0.84). The p-interaction between the pooled Hazard Ratio of both groups was 0.0551.

Conclusions: Both those younger and older than 65 years benefit from immunotherapy combined with chemotherapy in the treatment of non-small cell lung cancer. Although there appears to be greater efficacy in those younger than 65 years, the influence of age is not entirely clear.