0000000000710189
AUTHOR
Sabine Tejpar
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
Contains fulltext : 165965.pdf (Publisher’s version ) (Closed access) Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and speciali…
Integrative Genome-Scale DNA Methylation Analysis of a Large and Unselected Cohort Reveals 5 Distinct Subtypes of Colorectal Adenocarcinomas
BACKGROUND & AIMS: Colorectal cancer is an epigenetically heterogeneous disease, however, the extent and spectrum of the CpG island methylator phenotype (CIMP) is not clear. METHODS: Genome-scale methylation and transcript expression were measured by DNA Methylation and RNA expression microarray in 216 unselected colorectal cancers, and findings were validated using The Cancer Genome Atlas 450K and RNA sequencing data. Mutations in epigenetic regulators were assessed using CIMP-subtyped Cancer Genome Atlas exomes. RESULTS: CIMP-high cancers dichotomized into CIMP-H1 and CIMP-H2 based on methylation profile. KRAS mutation was associated significantly with CIMP-H2 cancers, but not CIMP-H1 can…
FCGR polymorphisms and cetuximab efficacy in chemorefractory metastatic colorectal cancer: an international consortium study
OBJECTIVE: We aimed to better clarify the role of germline variants of the FCG2 receptor, FCGR2A-H131R and FCGR3A-V158F, on the therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A large cohort with sufficient statistical power was assembled.DESIGN: To show a HR advantage of 0.6 in progression-free survival (PFS) for FCGR2A-HH versus the rest and FCGR3A-VV versus the rest, with an 80% power, 80 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type (KRAS-WT) and 52 KRAS-WT patients are required, respectively. This leads to a total sample size of 952 and 619 patients, respectively. Samples were collected from 1123 mCRC patients from 15 European centres treated wit…
PD-0024 Phase I/II Study of Folfiri Plus the MEK1/2 Inhibitor Pimasertib (MSC1936369B) as Second-Line Treatment for KRAS Mutated Metastatic Colorectal Cancer
ABSTRACT Introduction Pimasertib is a highly selective inhibitor of the MEK1/2 kinases of the MAPK pathway. It demonstrates potent antitumor activity in cell lines and xenograft models with activating (mainly BRAF and KRAS) mutations. A two-part study, comprising a safety run-in part followed by a randomized phase II part, was designed to investigate FOLFIRI plus pimasertib as second-line treatment for patients with KRAS mutated (mt) metastatic colorectal cancer (mCRC). The results of the safety run-in part, conducted primarily to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D), are reported here. Methods Patients with KRAS mt mCRC progressing on first-li…