Real-world efficacy and safety of sintilimab combined with nab-paclitaxel and S-1 as first-line treatment for locally advanced or metastatic pancreatic ductal adenocarcinoma: A single-center retrospective study.

Abstract

e16373 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and effective first-line treatment options remain limited. This study evaluated the real-world efficacy and safety of sintilimab combined with nab-paclitaxel and S-1 (AS) in patients with locally advanced or metastatic PDAC. Methods: This single-center retrospective study included patients with PDAC who were treated with sintilimab in combination with nab-paclitaxel and S-1 at Harbin Medical University Cancer Hospital between January 2023 and May 2025. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: A total of 37 patients were enrolled, with a median follow-up of 16.2 months. The median OS (mOS) was 12.2 months (95% CI, 9.9–14.5), and the median PFS (mPFS) was 8.6 months (95% CI, 5.6–11.6). All patients were evaluable for treatment response, with an ORR of 40.5% and a DCR of 91.9%. Four patients subsequently underwent curative-intent surgery, including one patient who achieved a pathological complete response (pCR). Exploratory circulating tumor DNA (ctDNA) methylation analysis in seven patients showed decreased methylation levels after two treatment cycles compared with baseline. Stratification according to CA19-9 trajectories at 6 weeks revealed significant differences in OS and PFS among patient subgroups (OS: P < 0.0001; PFS: P = 0.0001). Patients with a marked CA19-9 decline (≥50%) exhibited the most favorable survival outcomes (median OS not reached; median PFS, 10.2 months). Two patients experienced Grade ≥3 irAEs, which were manageable. The remaining irAEs were Grade 1–2, most commonly hypothyroidism (18.9%), elevated transaminases (5.4%), diarrhea (5.4%), and rash (5.4%). Conclusions: Sintilimab combined with nab-paclitaxel and S-1 demonstrated promising antitumor activity and an acceptable safety profile in patients with locally advanced or metastatic PDAC. Blood-based ctDNA methylation may serve as a potential predictive biomarker for treatment response. Further validation in large-scale phase III clinical trials is warranted.