| 1. |
- Guren, Tormod Kyrre, et al.
(författare)
-
Cetuximab in treatment of metastatic colorectal cancer : final survival analyses and extended RAS data from the NORDIC-VII study
- 2017
-
Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 116:10, s. 1271-1278
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis.Methods: A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations.Results: Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy.Conclusions: Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.
|
|
| 2. |
- Thomsen, Maria, et al.
(författare)
-
Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer
- 2016
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:46, s. 75013-75022
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. Results: High levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.0 versus 16.6 months, respectively (P < 0.001). Stratified according to increasing CRP levels, median OS varied from 24.3 months to 12.3 months, (P < 0.001). IL-6 and CRP levels affected overall prognosis also in adjusted analyses. The effect of IL-6 was particularly pronounced in patients with BRAF mutation (interaction P = 0.004). Materials and Methods: IL-6 and CRP were determined in pre-treatment serum samples from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progression-free survival (PFS) and overall survival (OS) was estimated. Conclusions: High baseline serum consentrations of IL-6 or CRP were associated with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status.
|
|
| 3. |
- Thomsen, Maria, et al.
(författare)
-
Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer : a BRAF-mutant subset with high CA 19-9 level and poor outcome
- 2018
-
Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 118:12, s. 1609-1616
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutation status of RAS and BRAF, as well as serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), are biomarkers used in clinical management of patients with gastrointestinal cancers. This study aimed to examine the prognostic role of these biomarkers in a patient population that started first-line chemotherapy for unresectable metastatic colorectal cancer (mCRC) in the NORDIC-VII study.METHODS: CEA and CA 19-9 were measured in serum samples from 545 patients obtained before the start of chemotherapy. Four hundred and ninety-four patients had detectable levels of carbohydrate antigen 19-9 (CA 19-9). RAS (exons 2-4) and BRAF (V600E) mutation status were available from 440 patients. Overall survival (OS) was estimated in patient groups defined by serum CEA or CA 19-9 levels using cut-off values of 5 mu g/L and 35 kU/L, respectively, in the total population and in subgroups according to RAS and BRAF mutation status.RESULTS: For both CEA and CA 19-9, elevated serum levels were associated with reduced OS in adjusted analyses which included RAS and BRAF mutation status, baseline World Health Organization performance status, and levels of alkaline phosphatase and C-reactive protein. The negative prognostic information provided by an elevated CA 19-9 level was particularly marked in patients with BRAF mutation (hazard ratio = 4.35, interaction P = 0.003, in an adjusted model for OS).CONCLUSIONS: High baseline serum concentrations of CEA and CA 19-9 provide independent information of impaired prognosis in mCRC. In patients with BRAF-mutant tumours, elevated serum CA 19-9 may identify a subgroup with highly aggressive disease and could contribute to improving therapeutic decisions.
|
|
