Search results for "Anti-EGFR"
showing 9 items of 9 documents
Does bevacizumab impact anti-EGFR therapy efficacy in metastatic colorectal cancer?
2016
IF 5.008; International audience; Anti-EGFR therapy and antiangiogenic therapies are used alone or in combination with chemotherapies to improve survival in metastatic colorectal cancer. However, it is unknown whether pretreatment with antiangiogenic therapy could impact on the efficacy of anti-EGFR therapy. We selected one hundred and twenty eight patients diagnosed with advanced colorectal cancer with a KRAS and NRAS unmutated tumor. These patients were treated with cetuximab or panitumumab alone or with chemotherapy as second or third-line. Univariate and multivariate Cox model analysis were performed to estimate the effect of a previous bevacizumab regimen on progression free survival a…
Prospective multicenter real-world RAS mutation comparison between OncoBEAM-based liquid biopsy and tissue analysis in metastatic colorectal cancer
2018
[EN] BACKGROUND: Liquid biopsy offers a minimally invasive alternative to tissue-based evaluation of mutational status in cancer. The goal of the present study was to evaluate the aggregate performance of OncoBEAM RAS mutation analysis in plasma of colorectal cancer (CRC) patients at 10 hospital laboratories in Spain where this technology is routinely implemented. METHODS: Circulating cell-free DNA from plasma was examined for RAS mutations using the OncoBEAM platform at each hospital laboratory. Results were then compared to those obtained from DNA extracted from tumour tissue from the same patient. RESULTS: The overall percentage agreement between plasma-based and tissue-based RAS mutatio…
Cancer stem cell-based models of colorectal cancer reveal molecular determinants of therapy resistance
2016
Abstract Colorectal cancer (CRC) therapy mainly relies on the use of conventional chemotherapeutic drugs combined, in a subset of patients, with epidermal growth factor receptor [EGFR]-targeting agents. Although CRC is considered a prototype of a cancer stem cell (CSC)-driven tumor, the effects of both conventional and targeted therapies on the CSC compartment are largely unknown. We have optimized a protocol for colorectal CSC isolation that allowed us to obtain CSC-enriched cultures from primary tumor specimens, with high efficiency. CSC isolation was followed by in vitro and in vivo validation, genetic characterization, and drug sensitivity analysis, thus generating panels of CSC lines w…
Phase 1 study of biweekly (Q2W) anti-EGFR monoclonal antibody (mAb) mixture Sym004 in patients (pts) with metastatic colorectal cancer (mCRC) resista…
2014
3551 Background: Preclinical models suggest that WT KRAS mCRC may retain EGFR dependency despite resistance developed to anti-EGFR mAb treatment (eg, cetuximab or panitumumab). Sym004 is the first-...
Proof-of-concept study of Sym004, an anti-EGFR monoclonal antibody (mAb) mixture, in patients (pts) with anti-EGFR mab-refractory KRAS wild-type (wt)…
2013
3551 Background: KRAS wt mCRC pts progressing on chemotherapy and anti-EGFR mAbs have limited treatment options. Sym004 is a first-in-class drug mixture of two mAbs targeting non-overlapping epitopes on the EGFR, causing its internalization and degradation. With this unique mechanism of action, Sym004 overcomes acquired resistance to anti-EGFR mAbs in preclinical studies. Methods: Open-label, multicenter trial assessing safety (primary endpoint) and efficacy of 2 dose levels of Sym004 in KRAS wt mCRC pts with prior clinical benefit to anti-EGFR mAbs and subsequent progression during or within 6 months after treatment cessation. Sym004 was administered until disease progression or unaccepta…
Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR…
2017
BACKGROUND: There is increasing evidence that metastatic colorectal cancer (mCRC) is a genetically heterogeneous disease and that tumours arising from different sides of the colon (left versus right) have different clinical outcomes. Furthermore, previous analyses comparing the activity of different classes of targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that primary tumour location (side), might be both prognostic and predictive for clinical outcome. METHODS: This retrospective analysis investigated the prognostic and predictive influence of the localization of the primary tumour in patients with unresectable RAS wt mCRC included in six randomized trials (CRY…
RECHALLENGE WITH ANTI-EGFR MONOCLONAL ANTIBODIES IN PRETREATED METASTATIC COLORECTAL CANCER PATIENTS: BEYOND THE LIMITS OF ACQUIRED RESISTANCE
2012
Background: Scientific data provide today the evidence that secondary K-RAS mutations do not occur during anti-EGFR therapy in CRC patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and Methods: we enrolled 39 irinotecan refractory patients who had a clinical benefit after a line of Cetuximab plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were re-treated with the same Cetuximab plus Irinotecan based therapy. Results: Median number of therapeutic lines before accrual was 4. Median inte…
Monoclonal antibodies and antibody fragments: state of the art and future perspectives in the treatment of non-haematological tumors
2011
Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies w…
Reduced-dose of doublet chemotherapy combined with anti-EGFR antibodies in vulnerable older patients with metastatic colorectal cancer: Data from the…
2022
Abstract Objectives To assess the toxicity patterns and effectiveness of doublet chemotherapy when administered at reduced doses of 20% (FOLFOX or FOLFIRI) in combination with anti-EGFR antibodies (cetuximab or panitumumab) in old, vulnerable patients with metastatic colorectal cancer (mCRC). Patients and methods We performed a retrospective observational study of RAS and BRAF wild-type, vulnerable patients aged ≥70 years with previously untreated mCRC. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results One hundred and eighteen patients were collected from 14 selected Italian centres.…