Neoadjuvant NASOX for pancreatic cancer: A prospective multicenter study.

Abstract

e16446 Background: Neoadjuvant therapy has become standard practice for selected patients with pancreatic cancer, with proven benefits in improving R0 resection rates and survival outcomes; nevertheless, optimal regimen selection remains poorly defined due to a lack of high-quality evidence. This study evaluated the efficacy and safety of the NASOX regimen—liposomal irinotecan, oxaliplatin, and S-1—as neoadjuvant therapy in patients with high-risk resectable, borderline resectable (BRPC), or locally advanced pancreatic cancer (LAPC). Methods: This ongoing prospective multicenter study enrolled patients with cytologically confirmed pancreatic cancer, an ECOG performance status of 0–2, adequate organ function, and no prior anticancer therapy. Patients received 4-6 cycles of neoadjuvant NASOX (liposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m 2 , S-1 40 mg/m 2 , every 2 weeks), with each cycle defined as 4 weeks and consisting of two administrations. Tumor response was assessed every 2 cycles according to RECIST v1.1, and serum CA19-9 levels were monitored biweekly. The primary endpoint was surgical conversion rate. Secondary end points included R0 resection rate, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between December 2023 and December 2025, 26 patients were enrolled (median age 58 years (range: 35–75); 34.6% females (n = 9)), including 1 (3.8%) high-risk resectable, 4 (15.4%) BRPC, and 21 (80.8%) LAPC. Among 18 patients with efficacy evaluation result, 8 achieved partial response (PR), 8 had stable disease (SD), and 2 had progressive disease (PD), yielding an ORR of 44.4% (8/18) and a DCR of 88.8% (16/18). Following multidisciplinary team (MDT) discussion, 7 patients were deemed suitable for surgical exploration; 2 declined surgery for non-medical reasons. 5 patients (25.0%) underwent resection, all achieving R0 resection. Median PFS and OS have not yet been reached. Among 16 patients completing planned therapy, median CA19-9 levels decreased from 580.9 U/mL at baseline to 213.5 U/mL; nine patients achieved > 50% reduction, and three normalized CA19-9 levels. Grade ≥3 treatment-related adverse events occurred in 38.5% of patients, most commonly neutropenia (19.2%) and vomiting (11.5%). No treatment-related deaths were observed. Conclusions: Neoadjuvant NASOX demonstrates promising antitumor activity with a manageable safety profile in patients with pancreatic cancer, supporting further prospective evaluation.