Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial

被引:18
作者
Conroy, T. [1 ,2 ]
Castan, F. [3 ]
Etienne, P. -l. [4 ]
Rio, E. [5 ]
Mesgouez-Nebout, N. [6 ]
Evesque, L. [7 ]
Vendrely, V. [8 ]
Artignan, X. [9 ]
Bouche, O. [10 ]
Gargot, D. [11 ]
Boige, V. [12 ]
Bonichon-Lamichhane, N. [13 ]
Louvet, C. [14 ]
Morand, C. [15 ]
de la Fouchardiere, C. [16 ]
Boileve, A. [12 ]
Delaye, M. [17 ]
Gourgou, S. [1 ]
Pezzella, V. [18 ]
Borg, C. [19 ]
机构
[1] Univ Lorraine, Inst Cancerol Lorraine, Nancy, France
[2] Univ Lorraine, INSERM, INSPIIRE, Nancy, France
[3] Univ Montpellier, Inst Reg Canc Montpellier, Montpellier, France
[4] Hop Prive Cotes Armor, CARIO, Plerin, France
[5] Inst Cancerol Ouest Site Rene Gauducheau, Saint-herblain, France
[6] Inst Cancerol Ouest Site Paul Papin, Angers, France
[7] Ctr Antoine Lacassagne, Nice, France
[8] Ctr Hosp & Univ Bordeaux, Hop Haut Leveque, Pessac, France
[9] Ctr Hosp Prive St Gregoire, St Gregoire, France
[10] Univ Reims, CHU Reims, Reims, France
[11] Ctr Hosp Blois, Blois, France
[12] Gustave Roussy, Villejuif, France
[13] Clin Tivoli, Bordeaux, France
[14] Inst Mutualiste Montsouris, Paris, France
[15] Ctr Hosp Dept Vendee, La Roche Sur Yon, France
[16] Ctr Leon Berard, Lyon, France
[17] Inst Curie, St Cloud, France
[18] R&D Unicanc, Paris, France
[19] Univ Hosp Besancon, CIC BT1431, Besancon, France
关键词
rectal cancer; chemoradiotherapy; neoadjuvant; FOLFIRINOX; III COLON-CANCER; ADJUVANT TREATMENT; COLORECTAL-CANCER; RANDOMIZED-TRIAL; 2ND CANCER; OPEN-LABEL; SURVIVAL; CHEMOTHERAPY; FOLFIRINOX; MULTICENTER;
D O I
10.1016/j.annonc.2024.06.019
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. Patients and methods: The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection fl ection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. Results: With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence fi dence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P = 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P = 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P = 0.033). The safety profile fi le remained unchanged since the previous analysis. Conclusions: Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed fi rmed long-term DFS and MFS benefits fi ts in LARC patients, and should be considered as one of the best options of care for these patients.
引用
收藏
页码:873 / 881
页数:9
相关论文
共 38 条
[1]   Restricted Mean Survival Time: An Obligatory End Point for Time-to-Event Analysis in Cancer Trials? [J].
A'Hern, Roger P. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (28) :3474-+
[2]   Improved Overall Survival With Oxaliplatin, Fluorouracil, and Leucovorin As Adjuvant Treatment in Stage II or III Colon Cancer in the MOSAIC Trial [J].
Andre, Thierry ;
Boni, Corrado ;
Navarro, Matilde ;
Tabernero, Josep ;
Hickish, Tamas ;
Topham, Clare ;
Bonetti, Andrea ;
Clingan, Philip ;
Bridgewater, John ;
Rivera, Fernando ;
de Gramont, Aimery .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (19) :3109-3116
[3]   Risk and location of distant metastases in patients with locally advanced rectal cancer after total neoadjuvant treatment or chemoradiotherapy in the RAPIDO trial [J].
Bahadoer, Renu R. ;
Hospers, Geke A. P. ;
Marijnen, Corrie A. M. ;
Peeters, Koen C. M. J. ;
Putter, Hein ;
Dijkstra, Esmee A. ;
Kranenbarg, Elma Meershoek-Klein ;
Roodvoets, Annet G. H. ;
van Etten, Boudewijn ;
Nilsson, Per J. ;
Glimelius, Bengt ;
van de Velde, Cornelis J. H. .
EUROPEAN JOURNAL OF CANCER, 2023, 185 :139-149
[4]   Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial [J].
Bahadoer, Renu R. ;
Dijkstra, Esmee A. ;
van Etten, Boudewijn ;
Marijnen, Corrie A. M. ;
Putter, Hein ;
Kranenbarg, Elma Meershoek-Klein ;
Roodvoets, Annet G. H. ;
Nagtegaal, Iris D. ;
Beets-Tan, Regina G. H. ;
Blomqvist, Lennart K. ;
Fokstuen, Tone ;
ten Tije, Albert J. ;
Capdevila, Jaume ;
Hendriks, Mathijs P. ;
Edhemovic, Ibrahim ;
Cervantes, Andres ;
Nilsson, Per J. ;
Glimelius, Bengt ;
van de Velde, Cornelis J. H. ;
Hospers, Geke A. P. .
LANCET ONCOLOGY, 2021, 22 (01) :29-42
[5]   Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER PRODIGE 23): Health-related quality of life longitudinal analysis [J].
Bascoul-Mollevi, Caroline ;
Gourgou, Sophie ;
Borg, Christophe ;
Etienne, Pierre-Luc ;
Rio, Emmanuel ;
Rullier, Eric ;
Juzyna, Beata ;
Castan, Florence ;
Conroy, Thierry .
EUROPEAN JOURNAL OF CANCER, 2023, 186 :151-165
[6]   Rectal Cancer, Version 2.2022 [J].
Benson, Al B., III ;
Venook, Alan P. ;
Al-Hawary, Mahmoud M. ;
Azad, Nilofer ;
Chen, Yi-Jen ;
Ciombor, Kristen K. ;
Cohen, Stacey ;
Cooper, Harry S. ;
Deming, Dustin ;
Garrido-Laguna, Ignacio ;
Grem, Jean L. ;
Gunn, Andrew ;
Hecht, J. Randolph ;
Hoffe, Sarah ;
Hubbard, Joleen ;
Hunt, Steven ;
Jeck, William ;
Johung, Kimberly L. ;
Kirilcuk, Natalie ;
Krishnamurthi, Smitha ;
Maratt, Jennifer K. ;
Messersmith, Wells A. ;
Meyerhardt, Jeffrey ;
Miller, Eric D. ;
Mulcahy, Mary F. ;
Nurkin, Steven ;
Overman, Michael J. ;
Parikh, Aparna ;
Patel, Hitendra ;
Pedersen, Katrina ;
Saltz, Leonard ;
Schneider, Charles ;
Shibata, David ;
Skibber, John M. ;
Sofocleous, Constantinos T. ;
Stotsky-Himelfarb, Eden ;
Tavakkoli, Anna ;
Willett, Christopher G. ;
Gregory, Kristina ;
Gurski, Lisa .
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2022, 20 (10) :1139-1167
[7]   Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: The EUROCARE study [J].
Brenner, Hermann ;
Bouvier, Anne Marie ;
Foschi, Roberto ;
Hackl, Monika ;
Larsen, Inger Kristin ;
Lemmens, Valery ;
Mangone, Lucia ;
Francisci, Silvia .
INTERNATIONAL JOURNAL OF CANCER, 2012, 131 (07) :1649-1658
[8]   NORAD01-GRECCAR16 multicenter phase III non-inferiority randomized trial comparing preoperative modified FOLFIRINOX without irradiation to radiochemotherapy for resectable locally advanced rectal cancer (intergroup FRENCH-GRECCAR- PRODIGE trial) [J].
Brouquet, Antoine ;
Bachet, Jean-Baptiste ;
Huguet, Florence ;
Karoui, Mehdi ;
Artru, Pascal ;
Sabbagh, Charles ;
Lefevre, Jeremie H. ;
Vernerey, Dewi ;
Mariette, Christophe ;
Vicaut, Eric ;
Benoist, Stephane .
BMC CANCER, 2020, 20 (01)
[9]   Incidence of second cancer within 5 years of diagnosis of a breast, prostate or colorectal cancer: a population-based study [J].
Cluze, Camille ;
Delafosse, Patricia ;
Seigneurin, Arnaud ;
Colonna, Marc .
EUROPEAN JOURNAL OF CANCER PREVENTION, 2009, 18 (05) :343-348
[10]   Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23) : a multicentre, randomised, open-label, phase 3 trial [J].
Conroy, Thierry ;
Bosset, Jean-Francois ;
Etienne, Pierre-Luc ;
Rio, Emmanuel ;
Francois, Eric ;
Mesgouez-Nebout, Nathalie ;
Vendrely, Veronique ;
Artignan, Xavier ;
Bouche, Olivier ;
Gargot, Dany ;
Boige, Valerie ;
Bonichon-Lamichhane, Nathalie ;
Louvet, Christophe ;
Morand, Clotilde ;
de la Fouchardiere, Christelle ;
Lamfichekh, Najib ;
Juzyna, Beata ;
Jouffroy-Zeller, Claire ;
Rullier, Eric ;
Marchal, Frederic ;
Gourgou, Sophie ;
Castan, Florence ;
Borg, Christophe .
LANCET ONCOLOGY, 2021, 22 (05) :702-715