Immunochemotherapy for Borderline Resectable or Locally Advanced Pancreatic Cancer: A Randomized Controlled Trial

Purpose The optimal treatment strategy for patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) remains undefined. We evaluated whether the addition of programmed cell death protein 1 blockade to modified FOLFIRINOX improves outcomes compared with modified FOLFIRINOX alone. Methods In this open-label, randomized phase II trial, patients with histologically confirmed BRPC or LAPC were randomly assigned (1:1) to receive modified FOLFIRINOX plus toripalimab (immunochemotherapy) or modified FOLFIRINOX alone (chemotherapy). Treatment response was assessed every 2 months, and surgical eligibility was determined by a multidisciplinary team. The primary end point was event-free survival (EFS) in the intention-to-treat population. Results Between April 2019 and March 2025, 392 patients were randomly assigned to immunochemotherapy (n = 196) or chemotherapy (n = 196). After a median follow-up of 39.6 months, immunochemotherapy significantly improved EFS compared with chemotherapy (median, 11.1 v 9.6 months; hazard ratio [HR], 0.74 [95% CI, 0.60 to 0.92]; P = .007). The median overall survival (OS) was 20.6 versus 17.1 months (HR, 0.81; 95% CI, 0.63 to 1.03). Objective response rates were 30.1% (59/196) and 18.9% (37/196), respectively. Tumor resection rates were 42.3% (83/196) and 43.9% (86/196), and R0 resection rates were 84.1% (69/82) and 74.7% (62/83), respectively. Prespecified subgroup analyses suggested improved EFS and OS in BRPC but not LAPC. Grade 3 or higher adverse events occurred in 47.9% (93/194) and 49.2% (96/195) of patients receiving immunochemotherapy and chemotherapy, respectively. Grade III or higher postoperative complications occurred in 30.1% (25/83) and 25.6% (22/86) of resected patients. Conclusion The addition of PD-1 blockade to modified FOLFIRINOX significantly improved EFS without increasing treatment-related toxicity or surgical morbidity in patients with BRPC or LAPC.