Adjuvant programmed death-1 inhibition combined with chemotherapy in resected pancreatic cancer: A real-world cohort study

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) carries a high risk of early recurrence even after curative resection. Although programmed death-1 (PD-1) inhibitors have shown limited efficacy in advanced PDAC-primarily due to its profoundly immunosuppressive tumor microenvironment-the adjuvant setting may provide an immunologically favorable window for PD-1 blockade. In this context, this real-world cohort study aimed to explore the efficacy and safety of PD-1 inhibitors combined with adjuvant chemotherapy in patients with resected PDAC. AIM To evaluate the efficacy and safety of PD-1 inhibitor–based adjuvant therapy combined with chemotherapy in patients with resected PDAC. METHODS We conducted a retrospective, single-center, real-world cohort study of 57 patients who underwent R0 or R1 resection for PDAC between 2021 and 2023. Patients received either adjuvant chemotherapy alone (n = 31) or chemotherapy combined with a PD-1 inhibitor (n = 26). The primary endpoint was recurrence-free survival (RFS); secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and treatment-related adverse events (TRAEs). Survival outcomes were analyzed using Kaplan-Meier estimates and multivariable Cox proportional hazards models. RESULTS Compared with chemotherapy alone, the addition of a PD-1 inhibitor significantly prolonged median RFS [21.0 months vs 9.0 months; hazard ratio (HR) = 0.37, 95% confidence interval (CI): 0.19-0.72; P = 0.003] and DMFS (21.0 months vs 11.0 months; HR = 0.33, 95%CI: 0.16-0.69; P = 0.003). Although OS was numerically longer in the combination group (27.0 months vs 21.0 months), the difference was not statistically significant (P = 0.293). Multivariable analysis identified PD-1 therapy, younger age, lower baseline creatinine, and early-stage disease as independent predictors of longer RFS. Subgroup analyses suggested a generally consistent RFS benefit across predefined clinical and biomarker-defined strata. Exploratory analyses indicated that dynamic reductions in carbohydrate antigen 19-9 levels and neutrophil-to-lymphocyte ratio were more frequently observed in the combination group. Grade ≥ 3 TRAEs occurred in 19.2% of the combination group and 25.8% of the chemotherapy group. CONCLUSION Adjuvant PD-1 blockade combined with chemotherapy was associated with improved recurrence-related outcomes in patients with resected PDAC without an increase in severe toxicity. These real-world findings provide clinical rationale for further prospective evaluation of immunotherapy-based adjuvant strategies and highlight the need for biomarker-informed randomized trials to validate these observations and optimize patient selection.