Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
04 May 2023
04 May 2023
Historique:
medline:
5
5
2023
pubmed:
3
5
2023
entrez:
3
5
2023
Statut:
ppublish
Résumé
In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival. We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability). A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67). Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).
Sections du résumé
BACKGROUND
BACKGROUND
In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.
METHODS
METHODS
We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).
RESULTS
RESULTS
A total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD-TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD-TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD-TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).
CONCLUSIONS
CONCLUSIONS
Among patients with refractory metastatic colorectal cancer, treatment with FTD-TPI plus bevacizumab resulted in longer overall survival than FTD-TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.).
Identifiants
pubmed: 37133585
doi: 10.1056/NEJMoa2214963
doi:
Substances chimiques
Bevacizumab
2S9ZZM9Q9V
Drug Combinations
0
Pyrrolidines
0
tipiracil
NGO10K751P
Trifluridine
RMW9V5RW38
Uracil
56HH86ZVCT
Banques de données
ClinicalTrials.gov
['NCT04737187']
EudraCT
['2020-001976-14']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1657-1667Subventions
Organisme : Servier
ID : N/A
Investigateurs
Arno Amann
(A)
Armin Gerger
(A)
Richard Greil
(R)
Birgit Gruenberger
(B)
Ulrich Popper
(U)
Gerald Prager
(G)
Thomas Winder
(T)
Koen Hendrickx
(K)
Ghislain Houbiers
(G)
Willem Lybaert
(W)
Marc Peeters
(M)
Eric Van Custem
(E)
Káthia Cristina Abdalla
(KC)
Arinilda Campos Bragagnoli
(A)
Roberto Carmagani Pestana
(R)
Felipe José Silva Melo Cruz
(FJSM)
Mauro Daniel Spina Donadio
(MD)
Gustavo Dos Santos Fernandes
(GDS)
Camila Motta Venchiarutti Moniz
(CMV)
Gabor Istvan Liposits
(GI)
Rene Olesen
(R)
Lone Nørgård Petersen
(LN)
Per Pfeiffer
(P)
Christophe Borg
(C)
Helene Boussion
(H)
Marie-Pierre Galais
(MP)
Pierre-Guillaume Poureau
(PG)
Julien Taieb
(J)
David Tougeron
(D)
Volker Heinemann
(V)
Jens Kisro
(J)
Dominik Paul Modest
(DP)
Ingo Schwaner
(I)
Péter Arkosy
(P)
György Bodoky
(G)
András Csejtei
(A)
Tibor Csöszi
(T)
Zsolt Horvath
(Z)
Zoltan Nagy
(Z)
Judith Olah
(J)
Zsuzsanna Pápai
(Z)
István Sipöcz
(I)
Antonio Avallone
(A)
Maria Banzi
(M)
Domenico Bilancia
(D)
Fortunato Ciardiello
(F)
Chiara Cremolini
(C)
Sara Lonardi
(S)
Evaristo Maiello
(E)
Nicola Personeni
(N)
Mario Scartozzi
(M)
Renata Duchnowska
(R)
Bartosz Itrych
(B)
Bogusława Karaszewska
(B)
Barbara Radecka
(B)
Wojciech Rogowski
(W)
Lucjan Wyrwicz
(L)
Piotr Wysocki
(P)
Mikhail Fedyanin
(M)
Dmitry Kirtbaya
(D)
Nikolay Kislov
(N)
Mikhail Kopp
(M)
Ludmila Lebedeva
(L)
Evgeny Ledin
(E)
Yulia Makarova
(Y)
Fedor Moiseenko
(F)
Rashida Orlova
(R)
Irina Radyukova
(I)
Tatiana Semiglazova
(T)
Daniil Stroyakovskyi
(D)
Sergei A Tjulandin
(SA)
Elena Élez
(E)
Reyes Ferreiro-Monteagudo
(R)
Cristina Grávalos-Castro
(C)
Eduardo Polo-Marqués
(E)
Vanessa Pachón Olmos
(V)
María José Ortiz-Morales
(MJ)
Fernando Rivera
(F)
María José Safont
(MJ)
Gemma Soler
(G)
Josep Tabernero
(J)
Manuel Valladares Ayerbes
(M)
Anna C Virgili Manrique
(AC)
Igor Bondarekno
(I)
Iryna Kolachko
(I)
Stepan Krulko
(S)
Yuriy Ostapenko
(Y)
Viktor Paramonov
(V)
Olga Ponomarova
(O)
Dinara Ryspayeva
(D)
Serhii Shevnia
(S)
Yaroslav Shparyk
(Y)
Tanios S Bekaii-Saab
(TS)
Ruemu E Birhiray
(RE)
Nafisa Burhani
(N)
Marcia Cruz-Correa
(M)
Mike Cusnir
(M)
Pratibha Desai
(P)
Marwan G Fakih
(MG)
Ryan Hall
(R)
Zhaohui Jin
(Z)
Jeremy C Jones
(JC)
Jonathan Lu
(J)
Nagendra Natarajan
(N)
Haroutioun Shahinian
(H)
Commentaires et corrections
Type : CommentIn
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