Neoadjuvant FOLF(IRIN)OX Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Multicenter Randomized Noncomparative Phase II Trial (PANACHE01 FRENCH08 PRODIGE48 study)
Authors: Lilian Schwarz, Jean-Baptiste Bachet, Aurelia Meurisse, Olivier Bouché, Eric Assenat, Guillaume Piessen, Pascal Hammel, Nicolas Regenet, Julien Taieb, Olivier Turrini, Francois Paye, Anthony Turpin, Francois-Regis Souche, Christophe Laurent, Reza Kianmanesh, Pierre Michel, Dewi Vernerey, Jean-Yves Mabrut, Celia Turco, Stephanie Truant, Antonio Sa Cunha, Eric Terrebonne, Angele Vienot, Nicolas Tabchouri, Fabienne Portales, Alain Sauvanet, Mickael Lesurtel, Olivia Hentic, Jean-Christophe Vaillant, Christope Tournigand, Rim Cherif, Emmanuel Buc, Caroline Petorin, Jean Christophe Souquet, Jean-Marc Regimbeau, Bruno Chauffert, Laurent Sulpice, Eveline Boucher, Thierry Andre, Stephane Benoist, Anne Thiro-Bidault, Ahmet Ayav, Laurence Choné, Jean Frederic Blanc, Maximiliano Gelli, David Malka, Yann Touchefeu, Vincent Moutardier, Laetitia Dahan, Emmanuel Mitry, Jean Lubrano, Karine Bouhier Leporrier, David Fuks, Christophe Louvet, David Tougeron, Jean-Pierre Richer, Emilia Ragot, Thierry Lecomte, Romain Coriat, Sebastien Gaujoux
Journal: Journal of Clinical Oncology (2025)

PURPOSE Despite limited RCTs, neoadjuvant chemotherapy (NAC) shows promise for resectable pancreatic adenocarcinoma (rPAC). Few prospective results are available on completing the full therapeutic sequence and oncologic outcomes with NAC. METHODS The PANACHE01-PRODIGE48 phase II trial randomly assigned 153 patients with rPAC (2:2:1) to four cycles of NAC (modified leucovorin, fluorouracil, irinotecan, and oxaliplatin [mFOLFIRINOX], arm 1; leucovorin, fluorouracil, and oxaliplatin [FOLFOX], arm 2) or up-front surgery (control) across 28 French centers (February 2017-July 2020). The primary objective was to evaluate the feasibility and efficacy of these NAC regimens. Two binary primary end points included 1-year overall survival (OS) postrandomization and the rate of patients completing the full therapeutic sequence. Event-free survival (EFS) assessed time to failure, defined as progression before surgery, unresectable/metastatic disease at surgery, recurrence, or death. RESULTS The primary objective was achieved for arm 1. In the intention-to-treat population, 70.8% (90% CI, 60.8 to 79.6) and 68% (90% CI, 55.5 to 78.8) completed the therapeutic sequence in arm 1 and arm 2, respectively. Within 12 months postrandomization, 84.3% (90% CI, 75.3 to 90.9) and 71.4% (90% CI, 59.0 to 81.8) of the patients were alive in arm 1 and arm 2, respectively. Treatment was safe and well-tolerated in both NAC arms. Arm 2 was stopped after interim analysis for lack of efficacy (H0 rejection for 1-year OS). One-year EFS rates were 51.4% (95% CI, 41.0 to 64.3), 43.1% (95% CI, 31.3 to 59.5), and 38.7% (95% CI, 24.1 to 62.0) in arm 1, arm 2, and control arm, respectively. CONCLUSION The feasibility and efficacy of mFOLFIRINOX in the perioperative setting are confirmed concerning therapeutic sequence completion and oncologic outcomes, supporting ongoing trials (PREOPANC3, Alliance AO21806). Further research is needed to identify patients who benefit from NAC (ClinicalTrials.gov identifier: NCT02959879 ; EudraCT: 2015-001851-65).