Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer
Authors: Conroy Thierry , Castan Florence , Lopez Anthony , Turpin Anthony , Ben Abdelghani Meher , Wei Alice C. , Mitry Emmanuel , Biagi James J. , Evesque Ludovic , Artru Pascal , Lecomte Thierry , Assenat Eric , Bauguion Lucile , Ychou Marc , Bouché Olivier , Monard Laure , Lambert Aurélien , Hammel Pascal ,   Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group, Francois Eric , Ramee Jean-François , Castanie Hélène , Pracht Marc , Ghiringhelli François , Maillard Emmanuel , Couffon Caroline , Volet Julien , Bourgeois Vincent , Chauvenet Marion , Blanc Jean-Frédéric , Péré-Vergé Denis , De La Fouchardiere Christelle , Adenis Antoine , El Hajbi Farid , Bennouna Jaafar , Texereau Patrick , Faroux Roger , Miglianico Laurent , Platini Christian , Legoux Jean-Louis , Caroli-Bosc François-Xavier , Bouhier-Leporrier Karine , Gagnaire Alice , Granger Victoire , Lebrun-Ly Valérie , Guimbaud Rosine , Touchefeu Yann , Gasmi Mohamed , Di Fiore Frédéric , Seitz Jean François , Etienne Pierre-Luc , Ligeza Poisson Catherine , Rinaldi Yves , Baba-Hamed Nabil , Bachet Jean Baptiste , Aparicio Thomas , Chone Laurence , Guillet Marielle , Forestier Julien , Terrebonne Eric , Hebbar Mohamed , Breysacher Gilles , Andre Thierry , Khemissa-Akouz Faiza , Hautefeuille Vincent , Guerin-Meyer Véronique , Hartwig Johannes , Becouarn Yves , Malka David , Louvet Christophe , Raoul Jean-Luc , Cany Laurent , Juzina Beata , Jouffroy Claire , Gourgou Sophie , Rassouli Mohammad , Chalchal Haji , Renouf Daniel , Wong Ralph , Lemay Frederic , Aubin Francine , Couture Felix , Mc Whirter Elaine , Welch Stephen , Kavan Petr , Findlay Brian , Cripps Christine , Cano Pablo , Ahmed Shahid , Harb Mohammed , Pressnail Bryn , Dowden Scott , O'Callaghan Chris 
Published: September 2022

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 &amp;lt; .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 &amp;lt; .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 &amp;lt; .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