Abstract
BackgroundImmunosenescence, 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.Results2,192 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.ConclusionsAmong 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.MethodsThe 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).
Highlights
The progress of immunotherapy, especially the programmed cell death protein-1 (PD-1) inhibitors, has created a major paradigm shift within the therapeutic landscape of several solid tumors [1,2,3]
Among patients aged over 75, no significantly prolonged overall survival was observed compared with chemotherapy
Nivolumab was associated with better overall survival (OS) in older non-small cell lung cancer (NSCLC) patients (≥65-year-age), and better progression-free survival (PFS) in all NSCLC patients
Summary
The progress of immunotherapy, especially the programmed cell death protein-1 (PD-1) inhibitors, has created a major paradigm shift within the therapeutic landscape of several solid tumors [1,2,3]. In the United States, the incidence of lung cancer was higher in older people based on a 2016 report, and mortality correlated with age of patients [6]. In the clinic, the efficacy and toxicity of chemotherapy was associated with age of nonsmall cell lung cancer (NSCLC) patients [7]. Previous research manifested that patients aged more than 75 years might not benefit from immune checkpoint inhibitors [8]. Immunosenescence, the age-related decline of immunity, affects the immune responses of non-small cell lung cancer (NSCLC) patients. 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
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