Bitte benutzen Sie diese Kennung, um auf die Ressource zu verweisen:
http://dx.doi.org/10.25673/108976
Langanzeige der Metadaten
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Ducreux, Michel | - |
dc.contributor.author | Tabernero, Josep | - |
dc.contributor.author | Grothey, Axel | - |
dc.contributor.author | Arnold, Dirk | - |
dc.contributor.author | O'Dwyer, Peter J. | - |
dc.contributor.author | Gilberg, Frank | - |
dc.contributor.author | Abbas, Alexander | - |
dc.contributor.author | Das Thakur, Meghna | - |
dc.contributor.author | Prizant, Hen | - |
dc.contributor.author | Irahara, Natsumi | - |
dc.contributor.author | Tahiri, Anila | - |
dc.contributor.author | Schmoll, Hans-Joachim | - |
dc.contributor.author | Van Cutsem, Eric | - |
dc.contributor.author | Gramont, Aimery | - |
dc.date.accessioned | 2023-07-12T10:53:37Z | - |
dc.date.available | 2023-07-12T10:53:37Z | - |
dc.date.issued | 2023 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/110931 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/108976 | - |
dc.description.abstract | Purpose: MODUL is an adaptable, signal-seeking trial of biomarker-driven maintenance therapy following first-line induction treatment in patients with metastatic colorectal cancer (mCRC). We report findings from Cohorts 1 (BRAFmut), 3 (human epidermal growth factor 2 [HER2]+) and 4 (HER2‒/high microsatellite instability, HER2‒/microsatellite stable [MSS]/BRAFwt or HER2‒/MSS/BRAFmut/RASmut). Methods: Patients with unresectable, previously untreated mCRC without disease progression following standard induction treatment (5-fluorouracil/leucovorin [5-FU/LV] plus oxaliplatin plus bevacizumab) were randomly assigned to control (fluoropyrimidine plus bevacizumab) or cohort-specific experimental maintenance therapy (Cohort 1: vemurafenib plus cetuximab plus 5-FU/LV; Cohort 3: capecitabine plus trastuzumab plus pertuzumab; Cohort 4: cobimetinib plus atezolizumab). The primary efficacy end-point was progression-free survival (PFS). Results: Cohorts 1, 3 and 4 did not reach target sample size because of early study closure. In Cohort 1 (n = 60), PFS did not differ between treatment arms (hazard ratio, 0.95; 95% confidence intervals 0.50–1.82; P = 0.872). However, Cohort 1 exploratory biomarker data showed preferential selection for mitogen-activated protein kinase (MAPK) pathway mutations (mainly KRAS, NRAS, MAP2K1 or BRAF) in the experimental arm but not the control arm. In Cohort 3 (n = 5), PFS ranged from 3.6 to 14.7 months versus 4.0 to 5.4 months in the experimental and control arms, respectively. In Cohort 4 (n = 99), PFS was shorter in the experimental arm (hazard ratio, 1.44; 95% confidence intervals 0.90–2.29; P = 0.128). Conclusions: Vemurafenib plus cetuximab plus 5-FU/LV warrants further investigation as first-line maintenance treatment for BRAFmut mCRC. MAPK-pathway emergent genomic alterations may offer novel therapeutic opportunities in BRAFmut mCRC. Cobimetinib plus atezolizumab had an unfavourable benefit:risk ratio in HER2‒/MSS/BRAFwt mCRC. New strategies are required to increase the susceptibility of MSS mCRC to immunotherapy. | eng |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | - |
dc.subject.ddc | 610 | - |
dc.title | Clinical and exploratory biomarker findings from the MODUL trial (Cohorts 1, 3 and 4) of biomarker-driven maintenance therapy for metastatic colorectal cancer | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | European journal of cancer | - |
local.bibliographicCitation.volume | 184 | - |
local.bibliographicCitation.pagestart | 137 | - |
local.bibliographicCitation.pageend | 150 | - |
local.bibliographicCitation.publishername | Elsevier | - |
local.bibliographicCitation.publisherplace | Amsterdam [u.a.] | - |
local.bibliographicCitation.doi | 10.1016/j.ejca.2023.01.023 | - |
local.subject.keywords | Biomarkers; BRAF; Cetuximab; Colorectal cancer; HER2; Maintenance therapy; Vemurafenib | - |
local.openaccess | true | - |
dc.identifier.ppn | 1852472634 | - |
local.bibliographicCitation.year | 2023 | - |
cbs.sru.importDate | 2023-07-12T10:52:58Z | - |
local.bibliographicCitation | Enthalten in European journal of cancer - Amsterdam [u.a.] : Elsevier, 1965 | - |
local.accessrights.dnb | free | - |
Enthalten in den Sammlungen: | Open Access Publikationen der MLU |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
---|---|---|---|---|
1-s2.0-S0959804923000473-main.pdf | 1.96 MB | Adobe PDF | ![]() Öffnen/Anzeigen |