Randomized phase 2 trial of immunochemotherapy for borderline resectable or locally advanced pancreatic cancer

The optimal treatment strategy for patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) is not clear. A randomized phase 2 trial at the First Affiliated Hospital of Zhejiang University (Hangzhou, China) evaluated addition of PD-1 blockade to modified (m) FOLFIRINOX. Patients with histologically confirmed BRPC or LAPC were randomized 1:1 to receive mFOLFIRINOX plus toripalimab (‘immunochemotherapy group’; n=196) or mFOLFIRINOX alone (‘chemotherapy group’; n=196). The primary endpoint was event-free survival (EFS). At a median follow-up of 39.6 months, immunochemotherapy significantly improved EFS compared with chemotherapy (median 11.1 versus 9.6 months; HR 0.74; p=0.007). The median overall survival (OS) was 20.6 versus 17.1 months (HR 0.81; 95% CI 0.63-1.03). Objective response rates were 30.1% and 18.9%, respectively. Tumor resection rates were 42.3% and 43.9%, and R0 resection rates were 84.1% and 74.7%, respectively. Prespecified subgroup analyses suggested improved EFS and OS in BRPC but not LAPC. Grade 3 or higher adverse events occurred in 47.9% of patients receiving immunochemotherapy and 49.2% of patients receiving chemotherapy, whereas grade 3 or higher postoperative complications occurred in 30.1% and 25.6% of resected patients. The authors conclude that addition of PD-1 blockade to mFOLFIRINOX signifcantly improved PFS without increasing treatment-related toxicity or surgical morbidity in patients with BRPC or LAPC.