Thromboembolic events during perioperative therapy for resectable and borderline resectable PDAC in the multicenter phase 3 PREOPANC-2 trial

Pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE). Although neoadjuvant treatment is increasingly used for PDAC, data on VTE in this setting are scarce. The multicenter phase 3 PREOPANC-2 trial by the Dutch Pancreatic Cancer Group evaluated VTE incidence during neoadjuvant and adjuvant therapy for resectable and borderline resectable PDAC and its relation to overall survival (OS). Patients were randomized to neoadjuvant 5-FU, leucovorin, irinotecan, and oxaliplatin followed by surgery (FFX arm) or neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine (CRT arm). VTE occurrence was retrospectively evaluated from randomization to 12 months later. VTE was diagnose in 28 of 325 patients (9%): nine preoperatively and nineteen postoperatively. Most VTEs were symptomatic (54%). Although a higher proportion of patients developed postoperative VTE in the CRT arm (FFX: 3% versus CRT: 12%; p=0.02), the 12-months cumulative incidence did not differ significantly between arms (6% versus 11%; p=0.06). Two patients died from PE-related causes in the CRT arm. VTE was independently associated with reduced OS (adjusted time-varying HR 2.13; p=0.002). The authors conclude that VTE occurred in 9% of patients with (borderline) resectable PDAC undergoing (neo)adjuvant treatment in the year after randomization and was associated with decreased OS.