Immunotherapy combined with chemotherapy versus chemotherapy alone in advanced pancreatic ductal adenocarcinoma: A real-world retrospective cohort study.

e16437 Background: Conventional chemotherapy remains the first-line standard for advanced pancreatic ductal adenocarcinoma (PDAC), while the benefit of combining immunotherapy with chemotherapy remains controversial. This retrospective study aimed to evaluate the efficacy, safety, and potential predictive biomarkers of first-line immuno-chemotherapy in advanced PDAC. Methods: We analyzed clinical data from 203 patients with advanced PDAC treated at the First Affiliated Hospital of Sun Yat-sen University. Patients were categorized into two groups: the chemotherapy-alone group (CT, n = 114) receiving nab-paclitaxel plus gemcitabine (AG) or (m)FOLFIRINOX, and the immuno-chemotherapy group (ICT, n = 89) receiving the same two chemotherapy regimens combined with PD-1/PD-L1 inhibitors. Comprehensive analysis included survival statistics, multivariable Cox regression, and exploratory biomarker assessments. Results: Patients in the ICT group had a significantly longer median overall survival (OS) than those in the CT group (19.2 vs. 14.3 months, Hazard Ratio [HR] = 0.62, p = 0.011). The 12-month progression-free survival (PFS) showed a significantly longer restricted mean survival time (RMST) in the ICT group compared with the CT group (RMST 0-12 = 8.61 vs. 7.13 months; difference = 1.48 months, 95% CI 0.36-2.60, p = 0.010). The disease control rate was significantly higher in the ICT group (86.5% vs. 63.2%, p < 0.001), while the overall response rate had no significant difference (16.8% vs. 15.8%, p = 0.839). No significant differences were observed in the incidence or severity of treatment-related adverse events (AEs) between the two groups. All immune-related AEs in the ICT group were mild to moderate (Grade 1-2). Biomarker exploration in a genomic subset (n = 67) identified TP53 mutation status as a significant modifier of treatment benefit, with TP53-mutant patients deriving substantial survival advantage from ICT (interaction HR = 0.19, p = 0.018). Conclusions: Compared to chemotherapy alone, first-line immuno-chemotherapy is associated with a significant improvement in overall survival in advanced PDAC, and may offer an early survival advantage. TP53 mutation may serve as a predictive biomarker for efficacy benefit from immune-chemotherapy, which supports the potential for future patient stratification strategies.