dc.contributor
Institut Català de la Salut
dc.contributor
[Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Taieb J] Georges Pompidou European Hospital, AP-HP, Paris-Cité University, SIRIC CARPEM Comprehensive Cancer Center, Paris, France. [Fakih M] City of Hope Comprehensive Cancer Center, Duarte, USA. [Prager GW] Department of Medicine I, Medical University of Vienna, Vienna, Austria. [Van Cutsem E] University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium. [Ciardiello F] University of Campania Luigi Vanvitelli, Naples, Italy
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Fakih, Marwan
dc.contributor.author
Prager, M.D., Gerald
dc.contributor.author
Van Cutsem, Eric
dc.contributor.author
Tabernero, Josep
dc.contributor.author
taieb, julien
dc.contributor.author
Ciardiello, Fortunato
dc.date.accessioned
2025-10-25T05:38:03Z
dc.date.available
2025-10-25T05:38:03Z
dc.date.issued
2024-03-20T07:59:48Z
dc.date.issued
2024-03-20T07:59:48Z
dc.identifier
Tabernero J, Taieb J, Fakih M, Prager GW, Van Cutsem E, Ciardiello F, et al. Impact of KRASG12 mutations on survival with trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer: post hoc analysis of the phase III SUNLIGHT trial. ESMO Open. 2024 Mar;9(3):102945.
dc.identifier
https://hdl.handle.net/11351/11212
dc.identifier
10.1016/j.esmoop.2024.102945
dc.identifier.uri
http://hdl.handle.net/11351/11212
dc.description.abstract
KRAS mutation; Metastatic colorectal cancer; Overall survival
dc.description.abstract
Mutació KRAS; Càncer colorectal metastàtic; Supervivència global
dc.description.abstract
Mutación KRAS; Cáncer colorrectal metastásico; Supervivencia global
dc.description.abstract
Background
In metastatic colorectal cancer (mCRC), KRAS mutations are often associated with poorer survival; however, the prognostic impact of specific point mutations is unclear. In the phase III SUNLIGHT trial, trifluridine/tipiracil (FTD/TPI) plus bevacizumab significantly improved overall survival (OS) versus FTD/TPI alone. We assessed the impact of KRASG12 mutational status on OS in SUNLIGHT.
Patients and methods
In the global, open-label, randomized, phase III SUNLIGHT trial, adults with mCRC who had received no more than two prior chemotherapy regimens were randomized 1 : 1 to receive FTD/TPI alone or FTD/TPI plus bevacizumab. In this post hoc analysis, OS was assessed according to the presence or absence of a KRASG12 mutation in the overall population and in patients with RAS-mutated tumors.
Results
Overall, 450 patients were analyzed, including 302 patients in the RAS mutation subgroup (214 with a KRASG12 mutation and 88 with a non-KRASG12 RAS mutation). In the overall population, similar OS outcomes were observed in patients with and without a KRASG12 mutation [median 8.3 and 9.2 months, respectively; hazard ratio (HR) 1.09, 95% confidence interval (CI) 0.87-1.4]. Similar OS outcomes were also observed in the subgroup analysis of patients with a KRASG12 mutation versus those with a non-KRASG12 RAS mutation (HR 1.03, 95% CI 0.76-1.4). FTD/TPI plus bevacizumab improved OS compared with FTD/TPI alone irrespective of KRASG12 mutational status. Among patients with a KRASG12 mutation, the median OS was 9.4 months with FTD/TPI plus bevacizumab versus 7.2 months with FTD/TPI alone (HR 0.67, 95% CI 0.48-0.93), and in patients without a KRASG12 mutation, the median OS was 11.3 versus 7.1 months, respectively (HR 0.59, 95% CI 0.43-0.81).
Conclusions
The presence of a KRASG12 mutation had no detrimental effect on OS among patients treated in SUNLIGHT. The benefit of FTD/TPI plus bevacizumab over FTD/TPI alone was confirmed independently of KRASG12 status.
dc.description.abstract
This work was supported by Servier International Research Institute (France) and Taiho Oncology, Inc. (USA) (no grant number).
dc.format
application/pdf
dc.relation
ESMO Open;9(3)
dc.relation
https://doi.org/10.1016/j.esmoop.2024.102945
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Anomalies cromosòmiques
dc.subject
Recte - Càncer - Tractament
dc.subject
Còlon - Càncer - Tractament
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Quimioteràpia combinada
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
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DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada
dc.title
Impact of KRASG12 mutations on survival with trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer: post hoc analysis of the phase III SUNLIGHT trial
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
