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Lancet2026;406(10522):2945-2956.December 20, 2026Journal Article

Preoperative mFOLFIRINOX versus PAXG for stage I-III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 × 2 factorial phase 3 trial.

Michele Reni1, Marina Macchini2, Giulia Orsi2, Letizia Procaccio3, Giuseppe Malleo4, Catia Carconi5, Ilario Giovanni Rapposelli6, Katia Bencardino7, Mario Scartozzi8, Gianpaolo Balzano9, Domenico Tamburrino10, Barbara Merelli11, Elisa Sperti12, Giulio Belfiori9, Nicole Liscia2, Silvia Bozzarelli13, Mariacristina Di Marco14, Emiliano Tamburini15, Michele Milella16, Sara Lonardi3, Giorgio Ercolani17, Michele Mazzola18, Diego Palumbo19, Valter Torri20, Massimo Falconi10
1Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: reni.michele@hsr.it.
2Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
3Oncology 1 Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
4Pancreatic Surgery Unit, Pancreas Institute, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
5Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
6Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy.
7Niguarda Cancer Center, Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
8Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
9Division of Pancreatic and Transplant Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Hospital, Milan, Italy.
10Vita-Salute San Raffaele University, Milan, Italy; Division of Pancreatic and Transplant Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Hospital, Milan, Italy.
11Oncology, Department of Oncology and Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy.
12SCDU Oncologia Medica, AO Ordine Mauriziano di Torino, Turin, Italy.
13Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy.
14Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy; Medical Oncology Unit, IRCSS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy.
15Department of Oncology and Palliative Care, Cardinale Giovanni Panico Hospital, Tricase, Italy.
16Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine, University of Verona, and Verona University and Hospital Trust, Verona, Italy.
17Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy; Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy.
18Division of Minimally-Invasive Surgical Oncology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
19Vita-Salute San Raffaele University, Milan, Italy; Department of Radiology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
20Clinical Oncology Department, Mario Negri Institute-IRCCS, Milan, Italy.
PubMed DOI

Abstract

BACKGROUND: Perioperative chemotherapy is a standard option for treatment of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the superiority of PAXG (cisplatin, nab-paclitaxel, capecitabine, and gemcitabine) over mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) in this population. METHODS: CASSANDRA…

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