Efficacy and safety of GVAX pancreas vaccine with CRS-207 in pretreated metastatic pancreatic adenocarcinoma: A systematic review and meta-analysis.

e15201 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, with low survival rates and oftentimes an advanced stage of detection. PDAC often shows limited benefits from conventional chemotherapy and poor response to immune checkpoint inhibitors due to immunosuppressive tumor microenvironments, making new immunotherapies a point of interest. One vaccine-based immunotherapy, the GM-CSF gene-transfected vaccine/ Listeria -based mesothelin-targeting vaccine (GVAX/CRS-207), has emerged as a potential approach to enhance antitumor immunity. Therefore, in this systematic review and meta-analysis, we aimed to evaluate the effectiveness of GVAX/CRS-207 in pretreated metastatic pancreatic adenocarcinoma. Methods: We searched PubMed, Cochrane Central, and Embase for randomized controlled trials (RCTs) involving adult patients with chemotherapy-pretreated metastatic pancreatic adenocarcinoma receiving the GVAX/CRS-207 regimen compared to a control (chemotherapy or placebo). Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using the Cochrane ROB 2.0 tool. Primary outcomes were overall survival (OS), progression-free survival (PFS), and safety/tolerability. Secondary outcomes included tumor response metrics and immune response. Pooled hazard ratios (HRs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Results: Three RCTs comprising 396 patients were included. The pooled analysis demonstrated no statistically significant improvement in overall survival for the GVAX/CRS-207 regimen compared to control (HR = 0.75, 95% CI: 0.30–1.92; P = 0.55). Pooled analyses for objective response rate (RR = 0.53, 95% CI: 0.06–4.79; P = 0.57) and disease control rate (RR = 1.48, 95% CI: 0.86–2.52; P = 0.15) also showed no significant benefit. Considerable heterogeneity was observed for survival outcomes (I² = 76–86%). The safety profile was acceptable, with the most common adverse events being low-grade, immune-related reactions such as pyrexia, fatigue, chills, and injection-site pain. Conclusions: In patients with pretreated metastatic pancreatic adenocarcinoma, the GVAX/CRS-207 prime-boost vaccine regimen was tolerable but did not confer a statistically significant improvement in overall survival (HR = 0.75, 95% CI: 0.30–1.92; P = 0.55) compared to control therapy. The available evidence is limited, and the high statistical heterogeneity observed among studies hinders definitive conclusions. Therefore, future research should focus on biomarker-driven patient selection and rational combination strategies to enhance vaccine efficacy.