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. 2025 Mar 1;11(3):276-287.
doi: 10.1001/jamaoncol.2024.5917.

Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX

Thomas F Stoop  1   2   3 , Toshitaka Sugawara  1   4 , Atsushi Oba  1   4   5 , Isabel M Feld  2   3 , Stijn van Roessel  2   3 , Eran van Veldhuisen  2   3 , Y H Andrew Wu  1   6   7 , Jo Nishino  8 , Mahsoem Ali  2   3 , Adnan Alseidi  9 , Alain Sauvanet  10 , Antonello Mirabella  11 , Antonio Sa Cunha  12 , Arto Kokkola  13 , Bas Groot Koerkamp  14 , Daniel Pietrasz  12 , Dyre Kleive  15 , Giovanni Butturini  16 , Giuseppe Malleo  17 , Hanneke W M van Laarhoven  3   18 , Isabella Frigerio  16 , Jeanne Dembinski  10 , Jin He  6   7 , Johan Gagnière  19 , Jörg Kleeff  20 , Jose M Ramia  21 , Keith J Roberts  22 , Knut J Labori  15 , Marco V Marino  11 , Massimo Falconi  23 , Michael B Mortensen  24 , Mickaël Lesurtel  12 , Morgan Bonds  9 , Nikolaos Chatzizacharias  22 , Oliver Strobel  25   26 , Olivier Turrini  27 , Oonagh Griffin  28 , Oskar Franklin  1   29 , Per Pfeiffer  30 , Richard D Schulick  1 , Roberto Salvia  17 , Roeland F de Wilde  14 , Safi Dokmak  10 , Salvador Rodriguez Franco  1 , Simone Augustinus  2   3 , Stefan K Burgdorf  31 , Stefano Crippa  23 , Thilo Hackert  25   32 , Timo Tarvainen  13 , William R Burns  6   7 , Wells Messersmith  33 , Johanna W Wilmink  3   18 , Richard A Burkhart  6   7 , Marco Del Chiaro  1 , Marc G Besselink  2   3 ; Scientific Committee of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and International Collaboration on Advanced Pancreatic Cancer
Collaborators, Affiliations

Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX

Thomas F Stoop et al. JAMA Oncol. .

Erratum in

  • Errors in Results and Figure 2.
    [No authors listed] [No authors listed] JAMA Oncol. 2025 Mar 1;11(3):354. doi: 10.1001/jamaoncol.2025.0295. JAMA Oncol. 2025. PMID: 40111309 Free PMC article. No abstract available.

Abstract

Importance: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Objective: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

Design, setting, and participants: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023.

Exposures: Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy.

Main outcomes and measures: The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS.

Results: Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypN0 disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03).

Conclusions and relevance: In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypN0.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Stoop reported grants from KWF Dutch Cancer Society, Deltaplan Alvleesklierkanker/Maag-Level-Darm Stichting, Cancer Center Amsterdam, and het Cultuurfonds outside the submitted work. Dr Oba reported grants from Bayer Yakuhin outside the submitted work. Prof Malleo reported personal fees from OncoSil Medical outside the submitted work. Dr van Laarhoven reported other support from speaking roles with Astellas, AstraZeneca, Beigene, BMC, Daiichi Sankyo, and Novartis paid to her institution, as well as grants from MyleoidTx, Incyte, Servier, ORCA, BMS, and Merck outside the submitted work. Dr Griffin reported grants from Health Research Board, Ireland during the conduct of the study. Dr Wilmink reported grants from MSD, Servier, and Nordic outside the submitted work. Dr Del Chiaro reported grants from Boston Scientific and Haemonetics outside the submitted work. No other disclosures were reported.

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