A comparison of mFOLFRINOX versus PAXG in pancreatic ductal adenocarcinoma

Data from the CASSANDRA trial, recently published on The Lancet, show a significant improvement in event-free survival for preoperative PAXG compared with mFOLFRINOX in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.

CASSANDRA trial is a randomized open-label Italian study that involved 132 adult patients with stage I-III resectable or borderline resectable pancreatic ductal adenocarcinoma. Participants were first randomly assigned PAXG (capecitabine, cisplatin, nab-paclitaxel and gemcitabine) or mFOLFIRINOX (fluorouracil, leucovorin, irinotecan and oxaliplatin) for 4 months, followed by a second randomization to 2 months of additional chemotherapy either before or after surgery. Event-free survival was 16 months with PAXG versus 10.2 months with mFOLFRINOX; moreover, PAXG not only prolongs event-free survival, but also increases the rate of disease control, pathological complete response and node- negative resections, and reduces the incidence of intra or early postoperative metastases. As authors point out, «According to subgroup analysis, the treatment effect consistently favoured PAXG across all the subpopulations. Furthermore, the PAXG regimen did not increase treatment-related toxicity and caused a clinically meaningful deterioration of quality of life in a smaller number of domains compared with mFOLFIRINOX. Neoadjuvant therapy should be indicated as standard-of-care for patients with non-metastatic pancreatic ductal adenocarcinoma before surgery. CASSANDRA sets PAXG as a new standard regimen for preoperative treatment of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma. Exploring the underlying biological mechanisms that guide the identification of the patients’ subgroups benefiting or not from preoperative therapy is a paramount important challenge», they conclude.