The effectiveness of PD-1 inhibitors in non-small cell lung cancer (NSCLC) patients of different ages

Abstract

Background: Immunosenescence, the age-related decline of immunity, affects the immune responses of non-small cell lung cancer (NSCLC) patients. Through immune responses, programmed death-1 (PD-1) inhibitors exert their antitumor robustness. In different ages of NSCLC patients, especially the older patients, the effectiveness of PD-1 inhibitors remains unclear. It is still controversial whether pembrolizumab or nivolumab should be used in treating NSCLC patients. Results: 2,192 NSCLC patients from four phase III RCTs were included. PD-1 inhibitors significantly prolonged the OS in both younger group (<65-year-age) (HR: 0.64, 95% CI: 0.54-0.75, P = 0.000) and older group (≥65-year-age) (HR: 0.68, 95% CI: 0.54-0.81, P = 0.001) than chemotherapy. Among patients aged over 75, no significantly longer OS was observed (HR: 1.02, 95% CI: 0.35-1.69, P = 0.971) than controls. In the older group (≥65-year-age), HR of OS favors nivolumab rather than pembrolizumab. Conclusions: Among patients aged over 75, no significantly prolonged overall survival was observed compared with chemotherapy. In comparison with pembrolizumab, nivolumab was associated with better OS in older NSCLC patients (≥65-year-age), and better PFS in all NSCLC patients. Older patients, especially those aged over 75, should be paid more attention to in the future clinical trials, guidelines, and clinical practice. Methods: The authors included clinical trials testing PD-1 inhibitors (nivolumab and pembrolizumab) compared with chemotherapies in older and younger patients. The authors used the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS).