Adjuvant Chemotherapy After Resection of Localized Pancreatic Adenocarcinoma Following Preoperative FOLFIRINOX
Authors: Stoop Thomas F. , Sugawara Toshitaka , Oba Atsushi , Feld Isabel M. , van Roessel Stijn , van Veldhuisen Eran , Wu Y. H. Andrew , Nishino Jo , Ali Mahsoem , Alseidi Adnan , Sauvanet Alain , Mirabella Antonello , Sa Cunha Antonio , Kokkola Arto , Groot Koerkamp Bas , Pietrasz Daniel , Kleive Dyre , Butturini Giovanni , Malleo Giuseppe , van Laarhoven Hanneke W. M. , Frigerio Isabella , Dembinski Jeanne , He Jin , Gagnière Johan , Kleeff Jörg , Ramia Jose M. , Roberts Keith J. , Labori Knut J. , Marino Marco V. , Falconi Massimo , B. Mortensen Michael , Lesurtel Mickaël , Bonds Morgan , Chatzizacharias Nikolaos , Strobel Oliver , Turrini Olivier , Griffin Oonagh , Franklin Oskar , Pfeiffer Per , Schulick Richard D. , Salvia Roberto , de Wilde Roeland F. , Dokmak Safi , Rodriguez Franco Salvador , Augustinus Simone , Burgdorf Stefan K. , Crippa Stefano , Hackert Thilo , Tarvainen Timo , Burns William R. , Messersmith Wells , Wilmink Johanna W. , Burkhart Richard A. , Del Chiaro Marco , Besselink Marc G. ,   Scientific Committee of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) and International Collaboration on Advanced Pancreatic Cancer, Jain Ajay , Saiura Akio , Balduzzi Alberto , Serrablo Alejandro , Coppola Alessandro , Zerbi Alessandro , Javed Ammar A. , Nikov Andrej , Halimi Asif , Bursics Attila , Janssen Boris V. , Miller Braden N. , Laurent Christophe , Mack Claudia E. , Hashimoto Daisuke , Caputo Damiano , Rangelova Elena , Sereni Elisabetta , Rückert Felix , Berrevoet Frederik , Balzano Giapaolo , Barauskas Giedrius , Belfiori Giulio , Fusai Giuseppe K. , Kazemier Geert , Alexandrino Henrique , Ishida Hirofumi , van Dam Jacob L. , Bachet Jean-Baptiste , Taieb Julien , Akahoshi Keiichi , Conlon Kevin C. , Tanaka Kimitaka , Dikmen Kürsat , Schwartz Lilian , Marthey Lysiane , Stommel Martijn W.J. , Varga Martin , House Michael G. , Tanabe Minoru , Al-Musawi Mohammed H. , Sugimoto Motokazu , Gotohda Naoto , Régenet Nicolas , Busch Olivier R. , Krohn Paul S. , Ghorbani Poya , Janssen Quisette P. , Bourdariat Raphael , Coriat Romain , van Dam Ronald M. , Pande Rupaly , Hirano Satoshi , Attila Szijarto , Klompmaker Sjors , Satoi Sohei , Keck Tobias , Yamamoto Tomohisa , Nakamura Toru , Nguyen Trang K. , Klaiber Ulla , Dubray Vincent , Bachu Vismaya , Inoue Yosuke , Takahashi Yu , Ishida Yuta , Aslami Zohra V. 
Published: January 2025

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.