Clinical Efficacy of Immune Checkpoint Inhibitors in Older Non-small-Cell Lung Cancer Patients: A Meta-Analysis

Abstract

Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape among non-small-cell lung cancer (NSCLC) patients. The efficacy of ICI therapy in older patients (≥65 years) is controversial and not fully clarified. We performed a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced or metastatic NSCLC based on age (<65 years vs. ≥65 years). Methods: A comprehensive literature search for eligible randomized control phase II/III trials that compared the efficacy of anti-PD-1/PD-L1 agents against chemotherapy in advanced or metastatic NSCLC patients. Pooled overall survival (OS) and progressionfree survival (PFS) estimates were calculated based on random/fixed effects models according to the heterogeneity between the studies. Results: A total of 10 studies involving 8 randomized controlled trials (2 updates) were enrolled in this meta-analysis [2,662 young patients (<65 years) and 1,971 older patients (≥65 years)]. The efficacy of anti-PD-1/PD-L1 agents is comparable between young (<65 years) and older (≥65 years) patients for OS [HR 0.75 95% CI (0.64-0.88) vs. 0.76 95% CI (0.66-0.87)]. However, our pooled analysis was not sufficient to show a significant benefit in terms of PFS for anti-PD-1/PD-L1 agents [HR 0.87 95% CI (0.74-1.01), P = 0.06]. In addition, we failed to see a PFS superiority of anti-PD-1/PD-L1 agents against chemotherapy in two age subgroups [<65 years and ≥65 years, HR 0.85 95% CI (0.72-1.01), P = 0.07 and HR 0.87 95% CI (0.68-1.10), P = 0.25]. Conclusion: ICIs therapy presents comparable efficacy in older advanced or metastatic NSCLC patients with young patients.

Prognostic impact of chronological age on efficacy of immune checkpoint inhibitors in non‐small‐cell lung cancer: Real‐world data from 86 173 patients

“…Consistently, the HR for death among patients with stage IV NSCLC aged ≥75 years who received ICIs was smaller than that among those who did not receive ICIs (1.23 vs. 1.32). These results suggest that aging does not negatively impact ICI efficacy in patients with stage IV NSCLC, in line with these previous reports 8,12,14–17 …”

“…An Italian multicenter retrospective study investigated the efficacy and safety of anti‐PD‐1 immunotherapy among patients with advanced NSCLC aged ≥75 years and found that the efficacy and toxicity of ICIs in elderly patients were comparable with the profiles observed in younger patients 14 . A meta‐analysis showed that ICI therapy and non‐ICI therapy of NSCLC had comparable efficacy in patients aged ≥65 years and those aged <65 years 15 . Another meta‐analysis of a large clinical dataset suggested that NSCLC patients aged ≥65 years can benefit even more from ICI therapy than younger patients 16 .…”

The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

“…First, a higher tumor mutation burden (TMB) was used for prediction of better durable clinical benefit (DCB) of immune checkpoint inhibitors (ICIs) in younger patients [ 37 ]. The poorer response of older patients to ICIs may be related to immunosenescence characterized by decreased T cell proliferation, which is considered an age-related change in the immunity of the host, suggesting that patients with increased age had a worse response to ICI therapy that may influence the efficacy of ICIs in elderly people with a high prevalence of malignancies [ 38 ]. Finally, treatment-related AEs occur less often in younger patients than in older patients.…”

Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration

“…In addition, some studies have shown that age is not an independent predictor of prognosis in cancer patients treated with ICIs. For example, Sun et al revealed that there was no significant difference in the OS of patients with NSCLC using PD-1/PD-L1 inhibitors between the young group (< 65 years old) and the old group (≥65 years old) (12). At the cutoff point of 70 years old, the PFS and OS of patients treated with ICIs in the melanoma, NSCLC and pan-cancer datasets were similar (13)(14)(15).…”