Abstract
Objectives Despite the fact that it is widely acknowledged that immune checkpoint inhibitors (ICIs) rely on the presence of immune response to take their antitumor effect, little is known whether there is an influence exerted on the efficacy of ICIs based on patients' age. We performed a systematic review and meta-analysis to explore the efficacy of ICIs between younger and older patients. Materials and Methods We searched online database and major conference proceedings for randomized controlled trials (RCTs) published of ICIs and included RCTs that conducted subgroup comparisons of age with available combination of hazard ratios (HRs) and 95% confidence interval (95%CI). Subsequently, we figured out the pooled HR and 95%CI in younger and older patients with a random-effects model and evaluated the within-study heterogeneity by using subgroup, sensitivity, and meta-regression analysis. Results and Conclusion A total of 12 eligible RCTs included in our study, which reported OS according to patients' age. The overall estimated random-effects for HR was 0.75 with 95% CI of 0.65-0.87 in younger arm versus 0.81 with 95% CI of 0.72-0.92 in older arm. ICIs can improve OS for patients with advanced or metastatic lung cancer when compared to controls, especially for those patients with NSCLC, anti-PD-1/PD-L1 inhibitors, non-squamous, Pembrolizumab or Atezolizumab used as well as subsequent-line setting, and the magnitude of benefit in OS had comparable efficacy in both younger and older arms using a cut-off of 65 yr. Conversely, we also drew a statically significant conclusion that older patients failed to acquire benefit from ICIs when subdivided with a further cut-off of 75 yr.
Highlights
Lung cancer, one of the most common malignant tumors, is currently the predominant cause of cancer-related deaths worldwide, which is responsible for more than 1.80 million deaths annually [1], and the 5-year survival rate has still remained poor at 16% [2]
This systematic review and meta-analysis came to the main conclusion being summarized as follows: immune checkpoint inhibitors (ICIs) have the ability to significantly prolong overall survival (OS) whether in younger or older arm, but the magnitude of this clinical benefit is age-dependent to a certain extent
Our analysis revealed that older patients received almost similar benefits with younger patients when treated with ICIs, but there is still a comparable OS benefit for ICIs in younger arm (
Summary
One of the most common malignant tumors, is currently the predominant cause of cancer-related deaths worldwide, which is responsible for more than 1.80 million deaths annually [1], and the 5-year survival rate has still remained poor at 16% [2]. Over half of patients with lung cancer have locally advanced or systemic metastasis leading to losing the opportunity for surgical resection. Platinumbased doublet chemotherapy and radiotherapy are often regarded as the primary choice for patients [3]. Even with these diversified therapies [4], the majority of lung patients will not acquire a satisfied prognosis. In recent years, the research on the antitumor activity of the immune system has resulted in the study and application of immunotherapy as the leading focus in lung cancer [5]. It has been embroiled in debate that if older patients may benefit less from immune checkpoint
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