Neoadjuvant FOLF(IRIN)OX Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Multicenter Randomized Noncomparative Phase II Trial (PANACHE01 FRENCH08 PRODIGE48 study)
Abstract
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).
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (60)
Lilian Schwarz
Dewi Vernerey, PhD, Methodology and Quality of Life in Oncology Unit, Centre Hospitalier Universitaire de Besançon, Besançon, France, Université Marie et Louis Pasteur, EFS, INSERM UMR1098 RIGHT, Besançon, France; Jean-Baptiste Bachet, MD, PhD, Sorbonne University, Hepatogastroenterology and Digestive Oncology Department, Pitié Salpêtrière Hospital, APHP, Paris, France; Antonio Sa Cunha, MD, PhD, Paris Saclay University, Centre Hépato-Biliaire, Department of HPB Surgery and Transplantation, Paul Brousse Hospital, APHP, Villejuif, France; and Lilian Schwarz, MD, PhD, Rouen University Hospital, Department of Digestive Surgery, Rouen, France, Normandie University, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Rouen, France
Jean-Baptiste Bachet
Aurelia Meurisse
Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
Olivier Bouche
Eric Assenat
Guillaume Piessen
Pascal Hammel
Nicolas Regenet
Department of Digestive Surgery, Centre Hospitalier Universitaire de Nantes, Nantes, France
Julien Taieb
Olivier Turrini
Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France
Francois Paye
Department of Surgery, Saint Antoine Hospital, Paris, France
Anthony Turpin
Francois-Regis Souche
Department of Digestive Surgical Oncology, University Hospital of Montpellier, Montpellier, France
Christophe Laurent
Department of Hepato-Bilio-Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, CHU de Bordeaux, Pessac, France
Reza Kianmanesh
Digestive Surgery Department, Centre Hospitalier Universitaire Robert Debré, Reims, France
Pierre Michel
Hepatogastroenterology Department, Rouen University Hospital, Rouen, France
Dewi Vernerey
Methodology and Quality of Life in Oncology Unit, Centre Hospitalier Universitaire de Besançon, Besançon, France
Jean-Yves Mabrut
University Hospital Lyon, Lyon, France
Celia Turco
Digestive Surgery Department, University Hospital of Besançon, Besançon, France
Stephanie Truant
Lille University Hospital, Lille, France
Antonio Sa Cunha
Eric Terrebonne
Angele Vienot
Nicolas Tabchouri
Fabienne Portales
Alain Sauvanet
Mickael Lesurtel
APHP Hopital Beaujon, Clichy, France
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 André
Stephane Benoist
Department of Digestive and Oncologic Surgery, Hôpital Bicêtre, APHP, Université Paris Sud, Le Kremlin-Bicêtre, France
Anne Thiro-Bidault
Ahmet Ayav
Laurence Choné
Jean Frederic Blanc
Hôpital Haut-Lévêque, CHU de Bordeaux, Service Hépato-Gastroentérologie et Oncologie Digestive, Bordeaux, France
Maximiliano Gelli
Université Paris-Saclay, Gustave Roussy, Villejuif, France
David Malka
Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France
Yann Touchefeu
Centre Hospitalier Universitaire de Nantes, Nantes, France
Vincent Moutardier
Laëtitia Dahan
Emmanuel Mitry
Medical Oncology Department, Institute Paoli-Calmettes, Marseille, France
Jean Lubrano
Karine Bouhier Leporrier
David Fuks
Christophe Louvet
Department of Medical Oncology, Institut Mutualiste Montsouris, Paris, France
David Tougeron
Department of Hepatology and Gastroenterology, Poitiers University Hospital, Poitiers, France
Jean-Pierre Richer
Emilia Ragot
Thierry Lecomte
Romain Coriat
Sebastien Gaujoux