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Do age and performance status matter? A systematic review and network meta-analysis of immunotherapy studies in

Maria Anna Siciliano1, Maria d'Apolito2, Teresa Del Giudice1

  • 1Oncology Unit, Oncology Department, "Azienda Ospedaliero Universitaria (AOU) Dulbecco" Hospital, Catanzaro, Italy.

Frontiers in Immunology
|October 9, 2025
PubMed
Abstract

Insights

Immune checkpoint inhibitors (ICIs) show varied effectiveness in non-small cell lung cancer (NSCLC) based on age and performance status. Tailored immunotherapy approaches are crucial, especially for elderly and frail patients.

Area of Science:

  • Oncology
  • Immunotherapy
  • Clinical Trials

Background:

  • Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment.
  • Efficacy in elderly/frail patients is uncertain due to immune-senescence and trial underrepresentation.

Purpose of the Study:

  • Evaluate and rank first-line ICI-based therapies in NSCLC.
  • Stratify efficacy by patient age and performance status (PS).

Main Methods:

  • Systematic review and meta-analysis of randomized controlled trials (RCTs).
  • Network meta-analysis (NMA) stratified by age (<65, ≥65, ≥75) and PS (0 vs. 1).
  • Endpoints: Overall Survival (OS) and Progression-Free Survival (PFS).

Main Results:

  • ICIs improved OS and PFS versus chemotherapy in most subgroups; no OS benefit in patients >75 years.
  • ICI+chemotherapy combinations were superior in younger patients; cemiplimab monotherapy showed promise in older/PS 1 patients.
  • Anti-PD-1 therapies outperformed anti-PD-L1 and anti-CTLA-4 therapies.

Conclusions:

  • ICI efficacy in advanced NSCLC is significantly influenced by age and PS.
  • Findings support personalized immunotherapy strategies.
  • Need for clinical trials in frail and elderly NSCLC populations.
Keywords:
checkpoint inhibitorsfrailnetwork meta-analysisnon-small cell lung canceroldersystematic review

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