Multicenter phase 3 trial of preoperative mFOLFIRINOX versus PAXG for stage I-III resectable or borderline resectable PDAC

Perioperative chemotherapy us a standard option for resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC). The phase 3 PACT-21 CASSANDRA trial, at 17 centers in Italy, compared PAXG (cisplatin, nab-paclitaxel, capecitabine, and gemcitabine) versus mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) in this population. In a 2x2 factorial design patients were randomized 1:1 to PAXG (n=132) or mFOLFIRINOX (n=128) for 4 months, followed by a second randomization to 2 months of additional chemotherapy either before or after surgery. The primary endpoint was event-free survival (EFS). PAXG prolonged the median EFS compared to mFOLFIRINOX (16.0 months versus 10.2 months; HR 0.63; p=0.0018). At least one grade 3 or worse event was observed in 66% of patients in the PAXG group and 61% of patients in the mFOLFIRINOX group, including one fatal event. The authors conclude that PAXG significantly improved EFS compared with mFOLFIRINOX in resectable or borderline resectable PDAC. Preoperative PAXG could be considered a standard option in this population.