Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study

doi:10.1038/s41416-025-03025-1

Comparative Study

. 2025 Jul;133(1):76-84.

doi: 10.1038/s41416-025-03025-1. Epub 2025 May 6.

Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study

Thomas F Stoop^#^{1

2

3}, Y H Andrew Wu^#^{4

5

6}, Atsushi Oba^#^{4

7

8}, Mahsoem Ali^{9

10}, Isabel M Feld^{11

9}, Mohammed H Al-Musawi¹², Ajay Jain¹³, Akio Saiura¹⁴, Alain Sauvanet¹⁵, Alessandro Coppola¹⁶, Ammar A Javed^{11

9

5

6

17}, Bas Groot Koerkamp¹⁸, Braden N Miller¹³, Daisuke Hashimoto¹⁹, Damiano Caputo^{20

21}, Dyre Kleive²², Elisabetta Sereni^{5

6

23}, Geert Kazemier^{9

10}, Giulio Belfiori²⁴, Hirofumi Ishida¹⁴, Jacob L van Dam¹⁸, Jeanne Dembinski¹⁵, Keiichi Akahoshi⁷, Keith J Roberts²⁵, Kimitaka Tanaka²⁶, Knut J Labori²², Massimo Falconi²⁴, Michael G House²⁷, Motokazu Sugimoto²⁸, Minoru Tanabe⁷, Naoto Gotohda²⁸, Nikolaos Chatzizacharias²⁵, Paul S Krohn²⁹, Safi Dokmak¹⁵, Salvador Rodriguez Franco⁴, Satoshi Hirano²⁶, Stefan K Burgdorf²⁹, Stefano Crippa²⁴, Sohei Satoi^{4

19}, Trang K Nguyen²⁷, Tomohisa Yamamoto²⁶, Toru Nakamura²⁶, Yuta Ushida⁸, Vismaya Bachu^{5

6}, William R Burns^{5

6}, Yosuke Inoue⁸, Yu Takahashi⁸, Zohra Aslami^{5

6}, Richard D Schulick⁴, Jin He^{5

6}, Wells Messersmith³⁰, Marc G Besselink^{11

9}, Richard A Burkhart^{5

6}, Johanna W Wilmink^{9

31}, Marco Del Chiaro⁴; International Consortium on Pancreatic Cancer Surgery and Oncology (ICON)

Collaborators, Affiliations

Collaborators

International Consortium on Pancreatic Cancer Surgery and Oncology (ICON):
Jacob L van Dam, Marco Del Chiaro, Boris V Janssen, Rupaly Pande, Oskar Franklin, Olivier R Busch, Hiroyuki Ishida, Toshitaka Sugawara, Roeland F de Wilde

Affiliations

¹ Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. t.f.stoop@amsterdamUMC.nl.
² Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands. t.f.stoop@amsterdamUMC.nl.
³ Cancer Center Amsterdam, Amsterdam, The Netherlands. t.f.stoop@amsterdamUMC.nl.
⁴ Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
⁵ Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁸ Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
⁹ Cancer Center Amsterdam, Amsterdam, The Netherlands.
¹⁰ Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
¹¹ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands.
¹² Clinical Trials of Office, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
¹³ Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
¹⁴ Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
¹⁵ Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, INSERM Unité Mixte de Recherche 1149, Clichy, France.
¹⁶ Dipartimento di Chirurgia Sapienza Università di Roma, Rome, Italy.
¹⁷ Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA.
¹⁸ Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁹ Department of Surgery, Kansai Medical University, Osaka, Japan.
²⁰ Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
²¹ Research Unit of General Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
²² Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²³ Department of General and Pancreatic Surgery, The Pancreas Institute University of Verona, Hospital Trust, Verona, Italy.
²⁴ Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy.
²⁵ Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, UK.
²⁶ Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan.
²⁷ Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁸ Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
²⁹ Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
³⁰ Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
³¹ Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands.

^# Contributed equally.

PMID: 40328917
PMCID: PMC12238338 (available on 2026-05-06)
DOI: 10.1038/s41416-025-03025-1

Comparative Study

Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study

Thomas F Stoop et al. Br J Cancer. 2025 Jul.

. 2025 Jul;133(1):76-84.

doi: 10.1038/s41416-025-03025-1. Epub 2025 May 6.

Authors

Collaborators

International Consortium on Pancreatic Cancer Surgery and Oncology (ICON):
Jacob L van Dam, Marco Del Chiaro, Boris V Janssen, Rupaly Pande, Oskar Franklin, Olivier R Busch, Hiroyuki Ishida, Toshitaka Sugawara, Roeland F de Wilde

Affiliations

¹ Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA. t.f.stoop@amsterdamUMC.nl.
² Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands. t.f.stoop@amsterdamUMC.nl.
³ Cancer Center Amsterdam, Amsterdam, The Netherlands. t.f.stoop@amsterdamUMC.nl.
⁴ Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
⁵ Division of Hepatobiliary and Pancreatic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁸ Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan.
⁹ Cancer Center Amsterdam, Amsterdam, The Netherlands.
¹⁰ Amsterdam UMC, Location Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands.
¹¹ Amsterdam UMC, Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands.
¹² Clinical Trials of Office, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
¹³ Division of Surgical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
¹⁴ Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
¹⁵ Department of HPB Surgery and Liver Transplantation, Hôpital Beaujon, University Paris Cité, INSERM Unité Mixte de Recherche 1149, Clichy, France.
¹⁶ Dipartimento di Chirurgia Sapienza Università di Roma, Rome, Italy.
¹⁷ Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA.
¹⁸ Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹⁹ Department of Surgery, Kansai Medical University, Osaka, Japan.
²⁰ Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
²¹ Research Unit of General Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
²² Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²³ Department of General and Pancreatic Surgery, The Pancreas Institute University of Verona, Hospital Trust, Verona, Italy.
²⁴ Pancreatic Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milano, Italy.
²⁵ Hepato-Pancreato-Biliary Unit, Department of Surgery, University Hospitals of Birmingham, Birmingham, UK.
²⁶ Department of Gastroenterological Surgery II, Hokkaido University, Faculty of Medicine, Hokkaido, Japan.
²⁷ Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁸ Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
²⁹ Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
³⁰ Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
³¹ Amsterdam UMC, Location University of Amsterdam, Department of Medical Oncology, Amsterdam, The Netherlands.

^# Contributed equally.

PMID: 40328917
PMCID: PMC12238338 (available on 2026-05-06)
DOI: 10.1038/s41416-025-03025-1

Abstract

Background: It remains unclear whether there is a difference in overall survival (OS) benefit between (m)FOLFIRINOX and gemcitabine-nab-paclitaxel as preoperative regimens for localised pancreatic adenocarcinoma. This study aimed to investigate the outcome of patients with resected localised pancreatic adenocarcinoma following (m)FOLFIRINOX versus gemcitabine-nab-paclitaxel.

Methods: International multicentre retrospective study (16 centres, 8 countries, 3 continents), including consecutive patients after pancreatic resection for localised pancreatic adenocarcinoma following 2-6 months preoperative (m)FOLFIRINOX or gemcitabine-nab-paclitaxel (2010-2018). Primary endpoint was OS from start of preoperative chemotherapy. Cox regression analysis was performed to investigate the association of the preoperative chemotherapy regimen with OS, adjusted for confounders at diagnosis.

Results: Overall, 935 patients were included after resection of localised pancreatic adenocarcinoma following preoperative (m)FOLFIRINOX (65%) or gemcitabine-nab-paclitaxel (35%). Preoperative chemotherapy regimen (m)FOLFIRINOX was not associated with OS (HR = 0.83 [95% CI 0.64-1.08]), compared to gemcitabine-nab-paclitaxel. Interaction analysis showed stronger effect of (m)FOLFIRINOX in patients with a lower (i.e., non-elevated/marginally elevated) serum CA19-9 at diagnosis (p_interaction = 0.032).

Conclusion: This international study found no OS benefit of preoperative (m)FOLFIRINOX in patients with resected localised pancreatic adenocarcinoma compared to gemcitabine-nab-paclitaxel.

PubMed Disclaimer

Conflict of interest statement

Competing interests: MDC has been awarded with an industry grant (Haemonetics, Inc) to conduct a multicenter study to evaluate the prognostic implications of TEG in pancreatic cancer. MDC is co-principal investigator of a Boston Scientific sponsored international multicenter study on the use of intraoperative pancreatoscopy of patients with IPMN. TFS, JWW, and MGB received two grants from Dutch Cancer Society (KWF) and Deltaplan Alvleesklierkanker for the Dutch PREOPANC-4 project on the multidisciplinary management of LAPC. TFS is granted by the Cultuurfonds (Jan de Ruijsscher/Pia Huisman Fonds) and Cancer Center Amsterdam. AO has been awarded with a grant (Bayer Yakuhin, Ltd.) to conduct an observation study to investigate the clinical impact of EOB-MRI. SS discloses receipt of research funding from Nihon Servier, Boston Scientific, and Amino-up co.jp. JWW received research grants from Servier, Nordic, and MSD. Ethics approval and consent to participate: The study procedures were reviewed and approved by the Colorado Multiple Institutional Review Board (COMIRB) (protocol #19-2972) at the University of Colorado. The need for informed consent was waived because of the retrospective nature of this study. A previously created dataset was used to identify patients for this study [31].

Cited by

The Landmark Series: Neoadjuvant Therapy for Resectable Pancreatic Cancer.
Cardell CF, Dekker EN, Katz MHG, Tzeng CD. Cardell CF, et al. Ann Surg Oncol. 2025 Sep;32(9):6467-6476. doi: 10.1245/s10434-025-17736-5. Epub 2025 Jul 7. Ann Surg Oncol. 2025. PMID: 40624308 Review.

References

1. Dekker EN, van Dam JL, Janssen QP, Besselink MG, DeSilva A, Doppenberg D, et al. Improved clinical staging system for localized pancreatic cancer using the ABC factors: a TAPS Consortium Study. J Clin Oncol. 2024;42:1357–67. 10.1200/JCO.23.01311. - PubMed
1. Oba A, Del Chiaro M, Satoi S, Kim SW, Takahashi H, Yu J, et al. New criteria of resectability for pancreatic cancer: a position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). J Hepatobiliary Pancreat Sci. 2022;29:725–31. 10.1002/jhbp.1049. - PubMed
1. Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, et al. Preoperative chemotherapy, radiotherapy, and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024;21:101–24. 10.1038/s41575-023-00856-2. - PubMed
1. Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O’Reilly EM, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:987–1002. 10.1016/j.annonc.2023.08.009. - PubMed
1. Tempero MA, Malafa MP, Benson AB, Cardin DB, Chiorean EG, Christensen JA, et al. Pancreatic Adenocarcinoma, Version 2.2024, NCCN clinical practice guidelines in oncology. National Comprehensive Cancer Network; 2024. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455.

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[1] Dekker EN, van Dam JL, Janssen QP, Besselink MG, DeSilva A, Doppenberg D, et al. Improved clinical staging system for localized pancreatic cancer using the ABC factors: a TAPS Consortium Study. J Clin Oncol. 2024;42:1357–67. 10.1200/JCO.23.01311. - PubMed

[2] Dekker EN, van Dam JL, Janssen QP, Besselink MG, DeSilva A, Doppenberg D, et al. Improved clinical staging system for localized pancreatic cancer using the ABC factors: a TAPS Consortium Study. J Clin Oncol. 2024;42:1357–67. 10.1200/JCO.23.01311. - PubMed

[3] Oba A, Del Chiaro M, Satoi S, Kim SW, Takahashi H, Yu J, et al. New criteria of resectability for pancreatic cancer: a position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). J Hepatobiliary Pancreat Sci. 2022;29:725–31. 10.1002/jhbp.1049. - PubMed

[4] Oba A, Del Chiaro M, Satoi S, Kim SW, Takahashi H, Yu J, et al. New criteria of resectability for pancreatic cancer: a position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). J Hepatobiliary Pancreat Sci. 2022;29:725–31. 10.1002/jhbp.1049. - PubMed

[5] Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, et al. Preoperative chemotherapy, radiotherapy, and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024;21:101–24. 10.1038/s41575-023-00856-2. - PubMed

[6] Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, et al. Preoperative chemotherapy, radiotherapy, and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024;21:101–24. 10.1038/s41575-023-00856-2. - PubMed

[7] Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O’Reilly EM, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:987–1002. 10.1016/j.annonc.2023.08.009. - PubMed

[8] Conroy T, Pfeiffer P, Vilgrain V, Lamarca A, Seufferlein T, O’Reilly EM, et al. Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:987–1002. 10.1016/j.annonc.2023.08.009. - PubMed

[9] Tempero MA, Malafa MP, Benson AB, Cardin DB, Chiorean EG, Christensen JA, et al. Pancreatic Adenocarcinoma, Version 2.2024, NCCN clinical practice guidelines in oncology. National Comprehensive Cancer Network; 2024. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455.

[10] Tempero MA, Malafa MP, Benson AB, Cardin DB, Chiorean EG, Christensen JA, et al. Pancreatic Adenocarcinoma, Version 2.2024, NCCN clinical practice guidelines in oncology. National Comprehensive Cancer Network; 2024. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1455.

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Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study

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Affiliations

Survival after neoadjuvant and induction FOLFIRINOX versus gemcitabine-nab-paclitaxel in patients with resected localised pancreatic adenocarcinoma: an international multicentre study

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Conflict of interest statement

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