Author(s): Thierry Conroy, MD1; Florence Castan, MSc2; Anthony Lopez, MD3; Anthony Turpin, MD, PhD4; Meher Ben Abdelghani, MD5; Alice C. Wei, MD, CM6; Emmanuel Mitry, MD, PhD7; James J. Biagi, MD8; Ludovic Evesque, MD9; Pascal Artru, MD10; Thierry Lecomte, MD, PhD11; Eric Assenat, MD, PhD12; Lucile Bauguion, MD13; Marc Ychou, MD, PhD14; Olivier Bouché, MD, PhD15; Laure Monard, PharmD16; Aurélien Lambert, MD1; Pascal Hammel, MD, PhD17; for the Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group
Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available.
To report 5-year outcomes and explore prognostic factors for overall survival.
DESIGN, SETTING, AND PARTICIPANTS
This open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization. Patients were included from April 16, 2012, through October 3, 2016. The cutoff date for this analysis was June 28, 2021.
A total of 493 patients were randomized (1:1) to receive treatment with modified FOLFIRINOX (oxaliplatin, 85 mg/m2 of body surface area; irinotecan, 150-180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 2400 mg/m2, every 2 weeks) or gemcitabine (1000 mg/m2, days 1, 8, and 15, every 4 weeks) as adjuvant therapy for 24 weeks.
MAIN OUTCOMES AND MEASURES
Primary end point was disease-free survival. Secondary end points included overall survival, metastasis-free survival, and cancer-specific survival. Prognostic factors for overall survival were determined.
Of the 493 patients, 216 (43.8%) were women, and the mean (SD) age was 62.0 (8.9) years. At a median of 69.7 months’ follow-up, 367 disease-free survival events were observed. In patients receiving chemotherapy with modified FOLFIRINOX vs gemcitabine, median disease-free survival was 21.4 months (95% CI, 17.5-26.7) vs 12.8 months (95% CI, 11.6-15.2) (hazard ratio [HR], 0.66; 95% CI, 0.54-0.82; P < .001) and 5-year disease-free survival was 26.1% vs 19.0%; median overall survival was 53.5 months (95% CI, 43.5-58.4) vs 35.5 months (95% CI, 30.1-40.3) (HR, 0.68; 95% CI, 0.54-0.85; P = .001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI, 14.0-21.2) (HR, 0.64; 95% CI, 0.52-0.80; P < .001); and median cancer-specific survival was 54.7 months (95% CI, 45.8-68.4) vs 36.3 months (95% CI, 30.5–43.9) (HR, 0.65; 95% CI, 0.51-0.82; P < .001). Multivariable analysis identified modified FOLFIRINOX, age, tumor grade, tumor staging, and larger-volume center as significant favorable prognostic factors for overall survival. Shorter relapse delay was an adverse prognostic factor.
CONCLUSIONS AND RELEVANCE
The final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma.
Author Affiliations1Medical Oncology department, Institut de cancérologie de Lorraine, Vandoeuvre-lès-Nancy, France and Université de Lorraine, APEMAC, équipe MICS, Nancy, France
2Biometry Department, ICM Regional Cancer Institute of Montpellier, Montpellier, France and Montpellier University, Montpellier, France
3Hepatogastroenterology department, University Hospital, Nancy, France
4Medical Oncology Department, University hospital, Lille, France and University of Lille, Lille, France
5Medical Oncology Department, ICANS, Strasbourg, France
6Surgery department, Princess Margaret Hospital, Toronto, Ontario, Canada
7Medical Oncology department, Institut Paoli-Calmettes, Marseille, France
8Department of Oncology, Queen’s University, Canada
9Medical oncology department, Centre Antoine-Lacassagne, Nice, France
10Hepatogastroenterology department, Hôpital Jean-Mermoz, Lyon, France
11Hepatogastroenterology department, Hôpital Trousseau, Tours, France and INSERM UMR 6239, Tours University, Tours, France
12Medical oncology department, Centre Hospitalier Universitaire de Saint-Eloi, Montpellier, France
13Hepatogastroenterology department, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon, France
14Oncology department, ICM Regional Cancer Institute of Montpellier, Montpellier, France and Montpellier University, Montpellier, France
15Digestive oncology department, Centre Hospitalier Universitaire Robert Debré, Reims, France
16R&D, Unicancer, Paris, France
17Digestive and Medical Oncology department, Hôpital Paul Brousse and University Paris-Saclay, Villejuif, France