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Clinical Trial
. 2022 Nov 1;8(11):1571-1578.
doi: 10.1001/jamaoncol.2022.3829.

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial

Thierry Conroy  1 , Florence Castan  2 , Anthony Lopez  3 , Anthony Turpin  4 , Meher Ben Abdelghani  5 , Alice C Wei  6 , Emmanuel Mitry  7 , James J Biagi  8 , Ludovic Evesque  9 , Pascal Artru  10 , Thierry Lecomte  11 , Eric Assenat  12 , Lucile Bauguion  13 , Marc Ychou  14 , Olivier Bouché  15 , Laure Monard  16 , Aurélien Lambert  1 , Pascal Hammel  17 ; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group
Collaborators, Affiliations
Clinical Trial

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial

Thierry Conroy et al. JAMA Oncol. .

Erratum in

  • Errors in Figure 1.
    [No authors listed] [No authors listed] JAMA Oncol. 2023 Jan 1;9(1):151. doi: 10.1001/jamaoncol.2022.6629. JAMA Oncol. 2023. PMID: 36416803 Free PMC article. No abstract available.

Abstract

Importance: 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.

Objective: 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.

Interventions: 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.

Results: 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.

Trial registration: EudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lopez reported grants from Roche as well as personal fees from Amgen, Vifor Pharma, Bayer, Merck, Sanofi, Ipsen, Servier, Pierre Fabre, Viatris, AbbVie, MSD, Novartis, and Mundi Pharma outside the submitted work. Dr Turpin reported grants from AstraZeneca as well as personal fees from Pierre Fabre, Merck Serono, and Viatris outside the submitted work. Dr Ben Abdelghani reported personal fees from Mylan, Amgen, Servier, Merck, Elivie, Amasante, Sanofi, and Mundipharma outside the submitted work. Dr Wei reported personal fees from Histosonics, AstraZeneca, Medtronic, Biosapien, Intuitive, and Bayer outside the submitted work. Dr Artru reported personal fees from Servier, Pierre Fabre, AstraZeneca, Amgen, and MSD outside the submitted work. Dr Lecomte reported personal fees from AstraZeneca outside the submitted work. Dr Bouché reported personal fees from Roche, Amgen, Pierre Fabre, Merck, Bayer, and Servier outside the submitted work. Dr Hammel reported personal grants and personal fees from AstraZeneca, Celgene, Erythec Pharma, Halozyme, Ipsen, Mylan, Rafael Pharmaceuticals, Servier, and Vect-Horus. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Analysis of Survival in the Intention-to-Treat Population
P values based on log rank test stratified by lymph node status, resection margins, and postoperative CA 19-9. mFOLFIRINOX indicates modified fluorouracil, leucovorin, irinotecan, and oxaliplatin; sHR, stratified hazard ratio.
Figure 2.
Figure 2.. Treatment Effect on Overall Survival in Subgroup Analyses
HR indicates hazard ratio; mFOLFIRINOX, modified fluorouracil, leucovorin, irinotecan, and oxaliplatin.
See this image and copyright information in PMC

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