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