Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/4016
Title: KRAS mutations are associated with inferior clinical outcome in patients with metastatic colorectal cancer, but are not predictive for benefit with cediranib
Authors: SMITH, John C.BROOKS, LauraHOFF, Paulo M.MCWALTER, GaelDEARDEN, SimonMORGAN, Shethah R.WILSON, DavidROBERTSON, Jane D.JUERGENMEIER, Juliane M.
Citation: EUROPEAN JOURNAL OF CANCER, v.49, n.10, p.2424-2432, 2013
Abstract: Purpose: The prognostic potential of KRAS mutations in advanced colorectal cancer (CRC) patients and the impact of KRAS mutation status on the effectiveness of chemotherapy or vascular endothelial growth factor (VEGF) signalling inhibitor therapy remain unclear. KRAS mutation status was evaluated retrospectively as a potential prognostic/predictive marker of clinical outcomes using tumour samples from patients with metastatic CRC receiving cediranib or placebo plus FOLFOX/XELOX in a Phase III trial (HORIZON II; NCT00399035). Methods: KRAS codon 12 and 13 mutation analyses were performed using a commercially available, allele-specific, amplification refractory mutation system (ARMS)-based polymerase chain reaction (PCR) assay. Retrospective analyses of progression-free survival (PFS) and overall survival (OS) according to KRAS mutation status were performed for patients randomised to cediranib 20 mg or placebo. Results: KRAS status was determined in 599/1076 patients (cediranib 20 mg, n = 285/502; cediranib 30 mg, n = 110/216; placebo, n = 204/358). Baseline characteristics were similar across KRAS mutant (n = 258; 24.0%), wild-type (n = 341; 31.7%) and status unknown (n = 477; 44.3%) groups. There was a trend towards improved PFS and OS in the wild-type versus mutant subgroups independent of treatment (cediranib 20 mg and placebo: PFS hazard ratio (HR) = 0.85 [median PFS: wild-type = 8.5 months; mutant = 8.3 months]; OS HR = 0.71 [median OS: wild-type = 20.9 months; mutant = 16.9 months]). Treatment effects were similar between KRAS subgroups for cediranib 20 mg versus placebo (PFS: wild-type HR = 0.78, mutant HR = 0.82; OS: wild-type HR = 0.92, mutant HR = 1.01). Conclusion: Data from this large randomised Phase III study show that KRAS codon 12/13 mutations have negative prognostic value in metastatic CRC patients receiving treatment with FOLFOX/XELOX, but KRAS mutation status is not predictive of treatment benefit with cediranib, using PFS or OS.
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Artigos e Materiais de Revistas Científicas - FM/MDR
Departamento de Radiologia - FM/MDR

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Instituto de Radiologia - HC/InRad

Artigos e Materiais de Revistas Científicas - LIM/24
LIM/24 - Laboratório de Oncologia Experimental


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