1685TiP - Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): A multicenter randomized controlled trial

Background

Surgical resection followed by adjuvant mFOLFIRINOX is the current standard of care for patients with resectable pancreatic cancer. The main concern with adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach.

Trial design

This is a multicentre, phase III, RCT that will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centres and three centres in Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² at day 1, followed by 46 hours continuous infusion of 5-fluorouracil 2400 g/m²) followed by surgery and 4 cycles of adjuvant mFOLFIRINOX. Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. Accrual started on September 7, 2021, and as of May 10, 2023, all centres are open for inclusion and 138 patients have been randomized.

Clinical trial identification

NCT04927780.

Editorial acknowledgement

Legal entity responsible for the study

Erasmus MC.

Funding

Dutch Cancer Society and ZonMw.

Disclosure

All authors have declared no conflicts of interest.