Immune checkpoint inhibitor doublets: Are they beneficial for older patients? A systematic review and meta-analysis

Abstract

Introduction: The introduction of immune checkpoint inhibitors (ICIs) has significantly transformed the treatment landscape for advanced malignancies. These inhibitors bolster the immune system's capacity to detect and destroy cancer cells. ICIs used in cancer immunotherapy are primarily categorized into two groups: anti-PD-1/L1 and anti-CTLA-4. The application of combination ICI therapy (ICI doublets) in older patients prompts questions about their relative efficacy compared to standard therapies, particularly in comparison to younger patient cohorts.

Materials and methods: This study involved an extensive review of literature from databases including PubMed, Embase, and the Cochrane Register of Controlled Trials. Our primary aim was to assess overall survival (OS) outcomes in a cohort of older patients, specifically those aged 65 and above, undergoing treatment for advanced cancers. The treatment modalities considered included ICI doublets, ICI monotherapy (alone or in combination with non-ICI drugs), and non-ICI therapies. The study aimed to compare the OS outcomes across these different therapeutic approaches.

Results: The analysis incorporated data from 18 trials, indicating that patients treated with ICI doublets exhibited a statistically significant improvement in OS compared to the control group (hazard ratio [HR] = 0.9, 95% confidence interval [CI] 0.84-0.96; P < 0.01). The addition of CTLA-4 inhibitors did not show significant advantages over anti-PD-1/L1 monotherapy (HR = 0.92, 95% CI 0.83-1.02; P = 0.13). When compared to non-ICI therapies, such as chemotherapy alone, ICI doublets demonstrated improved OS outcomes (HR = 0.89, 95% CI 0.82-0.97; P < 0.01).

Discussion: Our findings suggest that ICI doublets may offer a modest improvement in the outcomes of older cancer patients compared to non-ICI-based treatments. Consequently, the use of ICI doublets in older patients should be considered on an individual basis, prioritizing cases where there are clear advantages over conventional therapy. This study underscores the importance of developing personalized treatment strategies for older patients, necessitating a cautious and individualized approach in medication selection.

Keywords: Anti-CTLA-4; Anti-PD(L1); Combinations; Immune checkpoint inhibitors; Older; meta-analysis.