Chemotherapy for Older Adults with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis

<b>Background:</b> 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. <b>Methods:</b> 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). <b>Results:</b> 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; <i>I</i>² = 18%). Among chemotherapy-treated patients, OS (34 studies; HR 1.00, 95% CI 0.99-1.02; <i>I</i>² = 23%) and PFS (11 studies; HR 0.96, 95% CI 0.86-1.07; <i>I</i>² = 10%) did not differ by age. Combination chemotherapy demonstrated superior OS (13 studies; HR 0.66, 95% CI 0.54-0.80; <i>I</i>² = 86%) with substantial heterogeneity and PFS (7 studies; HR 0.63, 95% CI 0.53-0.74; <i>I</i>² = 30%) compared to monotherapy. FOLFIRINOX and gemcitabine plus nab-paclitaxel demonstrated comparable OS (8 studies; HR 0.98, 95% CI 0.90-1.05; <i>I</i>² = 60%) and PFS (2 studies; HR 0.97, 95% CI 0.92-1.02; <i>I</i>² = 0%). <b>Conclusions:</b> 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.