Search results for "KRAS"
showing 10 items of 232 documents
Panitumumab in combination with gemcitabine/cisplatin (GemCis) for patients with advanced kRAS WT biliary tract cancer: A randomized phase II trial o…
2015
4082 Background: Biliary tract cancer encompasses a group of genetically heterogeneous tumors. Panitumumab is a human EGFR inhibitor and has shown anti-tumor activity in RAS WT colorectal cancer. M...
KRAS mutation signature in colorectal tumors significantly overlaps with the cetuximab response signature.
2008
Abstract LB-220: Translational research with RG7160 (GA201) leads to a phase II clinical study in combination with FOLFIRI in 2nd line metastatic col…
2012
Abstract GA201 is a novel dual-acting humanized, engineered IgG1 anti-EGFR mAb designed to enhance ADCC in combination with signaling inhibition. Superior efficacy was demonstrated versus cetuximab in orthotopic CRC xenograft models. Preclinical data indicated an increase in macrophages (4-5 fold) and NK cells (2-3 fold) infiltration in tumors treated with GA201 compared to cetuximab. In a phase I clinical study objective responses and long lasting disease stabilizations were observed. A marked reduction in circulating NK cells and an increased infiltration of immune cells into skin rash was seen. Preliminary evidence of the enhanced ADCC capacity of GA201 was investigated in 25 third line …
In the literature: February 2018
2018
Non-invasive liquid biopsies may transform the management of patients with cancer. Circulating tumour DNA (ctDNA) derived from cancer cells can be identified in most patients with advanced cancer, representing a potential non-invasive source of tumour DNA. The analysis of ctDNA may be useful to genotype the cancer, to select treatment options and to monitor response to treatment. ctDNA is often at a low level in plasma, requiring highly sensitive and accurate assays for ctDNA analysis. ctDNA was detected and profiled together with primary tumour DNA obtained from surgical specimens in 40 patients with lung cancer with localised disease who were diagnosed at stages I–III and operated on with…
Final results of study 20050181: A randomized phase III study of FOLFIRI with our without panitumumab (pmab) for the second‑line treatment (tx) of me…
2012
3535 Background: The primary analysis of study 20050181 showed that in patients (pts) with wild-type (WT) KRAS mCRC, pmab plus FOLFIRI given as second-line therapy significantly improved progression-free survival (PFS) vs FOLFIRI alone. Here, we report on a prespecified descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts with mCRC, ECOG 0-2, who had one prior fluoropyrimidine-based chemotherapy regimen were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI (Arm 2). Co-primary endpoints were OS and PFS (central assessment). Secondary endpoints included objective response rate (ORR) and safety. Tumor KRAS status was determined by a blin…
Evaluation of survival across several treatment lines in metastatic colorectal cancer: Analysis of the FIRE-3 trial (AIO KRK0306).
2017
Abstract Background We explored the impacts of sequential application of various treatment lines on survival kinetics. Therefore, differences in overall survival (OS) observed in FIRE-3 were investigated in the context of time and exposure to applied treatment. Patients and methods OS analyses (stratified by treatment with FOLFIRI plus either cetuximab or bevacizumab) were performed according to time intervals as well as using a Cox model to define changes of hazard ratio (HR) over time. Results The fraction of patients with systemic treatment and time on treatment markedly decreases over treatment lines and time. OS evaluation by a Cox model indicated a trend towards a non-proportional haz…
Treatment until progression: Data of the “on-treatment” population of the FIRE-3 (AIO KRK-0306) study.
2015
3589 Background: The FIRE-3 study (AIO KRK-0306) was designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. Overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Methods: In this exploratory analysis outcome parameters were calculated in dependence of progression during antibody treatment. As reported before by Saltz et al. (ASCO GI 2007) an “on study treatm…
Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance
2021
Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high-throughput coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs (n total = 95). Incident cancers presented with lower UICC and T stage compared to prevalent cancers (p <
Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?
2010
An important molecular target for metastatic CRC treatment is the epidermal growth factor receptor (EGFR). Many potential biomarkers predictive of response to anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have been retrospectively evaluated, including EGFR activation markers and EGFR ligands activation markers. With regard to the "negative predictive factors" responsible for primary or intrinsic resistance to anti-EGFR antibodies a lot of data are now available. Among these, KRAS mutations have emerged as a major predictor of resistance to panitumumab or cetuximab in the clinical setting and several studies of patients receiving first and subsequent lines of treatment have sho…
Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/Wo…
2010
The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC. 21 Suppl 6 vi1 10