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  • An update on the role of immune checkpoint inhibitors in lung cancer: a narrative systematic review
    Publication . Sousa, Inês; Martins, Diana; Mendes, Fernando
    Introduction: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, and its aggressive nature necessitates the development of alternative therapeutic strategies. Immune checkpoint inhibitors (ICIs) have shown remarkable success in LC treatment. Despite advances with programmed cell death protein-1/programmed cell death ligand-1 inhibitors, many patients experience limited or short-lived responses, prompting interest in novel ICIs such as T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain (TIGIT), lymphocyte-activation gene 3 (LAG-3), and indoleamine 2,3-dioxygenase 1 (IDO-1). Objectives: This narrative systematic review aimed to assess the clinical efficacy and safety of these novel ICIs compared to standard ICI therapy in LC. Methods: A systematic literature search was conducted across PubMed, Web of Science, and ClinicalTrials.gov. The search covered studies published from January 2020 to January 2025, to identify randomized controlled trials (RCTs) evaluating novel ICIs in LC. Due to substantial heterogeneity in study design, intervention targets, and outcome reporting, findings were synthesized narratively in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using RoB 2. Results: Five RCTs involving a total of 825 patients were included. TIGIT inhibition demonstrated benefit in progression-free survival and response rate. LAG-3 inhibitors showed mixed efficacy, with potential dose-related differences. IDO-1 inhibitors failed to improve outcomes compared with standard ICI. Reporting quality varied, with concerns regarding incomplete outcome data in some trials. Conclusion: These findings suggest promise for novel ICIs but are limited by small study numbers, methodological bias, and clinical heterogeneity. Larger, well-designed Phase III trials are required to validate these results.
    2025-12-18Text Open access Show more