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

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).

Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis

“…We also showed that IO-chemotherapy significantly improved OS both in patients < 65 years old (HR 0.46; P < .001) and ≥ 65 years old (HR 0.69; P = .008), with greater benefit in in younger patients (interaction P = .038). This finding is different from previous meta-analyses which revealed similar efficacy with immune checkpoint inhibitor monotherapy in patients younger vs. older than 65 years old [31, 32]. These results are clinically relevant because a majority of lung cancer patients were diagnosed at older ages and were often with poor performance status in real world [33].…”

High expression of Copine�1 promotes cell growth and metastasis in human lung adenocarcinoma

“…Despite improvements in therapeutic strategies, the survival and outcome of patients with NSCLC have not been markedly affected ( 4 ). The majority of patients have progressed to the advanced stage of the disease when the diagnosis is confirmed, which is beyond the optimal treatment period ( 18 ). Therefore, it is essential to elucidate the pathogenesis of NSCLC and to identify novel treatment targets.…”

Impact of smoking on efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer patients: a meta-analysis

“…Hence, using ICIs that block the cross talk of PD-L1 molecules and PD-1 molecules may inhibit tumor cells from evading the immunoreaction under this situation. Latest studies reveal that the efficacy of PD-1/PD-L1 inhibitors may correlate with sex and age; 4 , 5 however, little is known whether it is associated with the status of smoking.…”