Chemotherapy for Older Adults with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma: A Systematic...

Background: Treatment decisions for older adults with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) often rely on heterogeneous observational evidence and clinical judgment regarding survival benefits, regimen intensity, and tolerability. Methods: We systematically searched Embase, PubMed, and Scopus from inception to 30 March 2025, for studies reporting overall survival (OS) and/or progression-free survival (PFS) in older adults with advanced PDAC receiving systemic chemotherapy, as well as age-stratified outcomes among chemotherapy-treated patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were primarily extracted from multivariable-adjusted analyses. In cases without reported HRs, estimates were derived from summary statistics or Kaplan-Meier curves. The review protocol was registered in PROSPERO (CRD420261292913). Results: A total of 40 predominantly retrospective studies were included. Chemotherapy was associated with improved OS compared to best supportive care in older adults (9 studies; HR 0.46, 95% CI 0.39-0.54; I² = 18%). Among chemotherapy-treated patients, OS (34 studies; HR 1.00, 95% CI 0.99-1.02; I² = 23%) and PFS (11 studies; HR 0.96, 95% CI 0.86-1.07; I² = 10%) did not differ by age. Combination chemotherapy demonstrated superior OS (13 studies; HR 0.66, 95% CI 0.54-0.80; I² = 86%) with substantial heterogeneity and PFS (7 studies; HR 0.63, 95% CI 0.53-0.74; I² = 30%) compared to monotherapy. FOLFIRINOX and gemcitabine plus nab-paclitaxel demonstrated comparable OS (8 studies; HR 0.98, 95% CI 0.90-1.05; I² = 60%) and PFS (2 studies; HR 0.97, 95% CI 0.92-1.02; I² = 0%). Conclusions: Among carefully selected older adults with advanced PDAC, chemotherapy was associated with improved survival compared to supportive care. Chronological age did not predict outcomes, highlighting the need for geriatric-informed prospective trials.