Observational study on conditions for access to the analysis of KRAS mutation in patients with metastatic colorectal cancer receiving panitumumab treatment
CRLC Val-d'Aurelle, service de pathologie, parc Euromédecine, Montpellier, France. Bulletin du cancer
(Impact Factor: 0.6).
06/2012; 99(7-8):743-51. DOI: 10.1684/bdc.2012.1612
KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-Epidermal Growth Factor Receptor (EGFR) antibodies, such as cetuximab or panitumumab. KRAS mutations are unambiguously linked to a lack of response to these targeted therapies. Because of the major clinical impact of KRAS status, an observational study has been designed in France, focusing on the ability to perform KRAS testing between october 2008 and october 2009. The study was retro-prospective, national, multicentric, descriptive and non interventional, concerning public and private institutions and KRAS non mutated patients treated with panitumumab. The primary objective of this study was to evaluate delays between the genotyping KRAS request and the result. Secondary objectives were: type of genotyping requests (systematic/prospective or specific/retrospective), prevalence of the different genotyping techniques, delays between the genotyping KRAS request and therapy with panitumumab. Overall, 329 patients from 66 centres have been included. About half of them belonged to private institutions. The results were obtained with a mean delay of 33.4 ± 39.8 days (CI 95%: [28.8; 37.9] days; median: 24 days). Most of KRAS genotyping tests were performed on specific requests (65.3%), from a primary tumor (80.4%) and from a surgical specimen (73.9%). The more frequently used techniques for KRAS genotyping were: real time PCR (36.2%), sequencing (24.8%) and pyrosequencing (13.2%). This study emphasizes the functionality of cancer molecular genetic platforms dedicated to KRAS genotyping, which allow the use of molecular predictive biomarkers by different medical institutions. This study also underlines the broad spectrum of genotyping techniques (no consensus). The delays of response are still longer than expected but might be improved by optimizing the procedures.
Available from: Wenancjusz Domagala
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ABSTRACT: Identifying targets for personalized targeted therapy is the pathologist's domain and a treasure. For decades, pathologists have had to learn, understand, adopt and implement many new laboratory techniques as they arrived on the scene. Pathologists successfully integrate the results of those tests into final pathology reports that were, and still are, the basis of clinical therapeutic decisions. The molecular methods are different but no more difficult to comprehend in the era of "kit procedures". In recent years, the development of targeted therapies has influenced routine practices in pathology laboratories because the use of molecular techniques is required to include clinically useful predictive information in the pathology report. Pathologists have the knowledge and expertise to identify particular gene mutations using the appropriate molecular tests currently available. This review focuses on the most important recent developments in KRAS mutation testing in metastatic colorectal cancer (CRC), and shows that a pathologist is involved in 10 stages of this procedure. Recent studies have shown that highly sensitive, simple, reliable and rapid assays may significantly improve the identification of CRC patients resistant to anti-EGFR therapy. Thus, direct sequencing does not seem to be an optimal procedure of KRAS testing for clinical purposes. Twelve currently available high-sensitivity diagnostic assays (with the CE-IVD mark) for KRAS mutation testing are briefly described and compared. The suggested pathology report content for somatic mutation tests is described. In conclusion, evidence is presented that sending away paraffin blocks with tumor tissue for KRAS mutation testing may not be in the best interest of patients. Instead, an evidence-based approach indicates that KRAS mutation testing should be performed in pathology departments, only with the use of CE-IVD/FDA-approved KRAS tests, and with the obligatory, periodic participation in the KRAS EQA scheme organized by the European Society of Pathology as an independent international body.
Available from: vestnikramn.spr-journal.ru
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The detection of KRAS mutations is mandatory to initiate an anti-epidermal growth factor receptor (EGFR) antibody in the treatment of metastatic colorectal carcinoma (mCRC).
Patients and methods:
This observational retrospective study was performed in 160 French centres during a 2-week period in 2011. Its main objective was to evaluate the rate of KRAS testing in patients with mCRC having initiated their first-line therapy. Secondary objectives included time of process, techniques used and reasons for non-prescription.
Five hundred and thirty eight mCRC patients (67.1 ± 11.3 years, synchronous metastases: 69.9%) were enrolled in the study. KRAS testing was prescribed in 81.1% of patients, in a median of 15 days after the diagnosis of metastases, and of 15 days prior to the initiation of the first-line metastatic chemotherapy. KRAS status was available for 87% of patients, after 23.6 ± 28.2 days, but after the choice of the first-line therapy in 56.6% of patients. Heterogeneity of reception time was noteworthy within regions (8.3 ± 7 days to 38.8 ± 101 days). KRAS testing was not prescribed mainly due to the planned non-prescription of an anti-EGFR antibody.
This study confirmed that KRAS testing is definitely part of the management of most of mCRC patients, despite discrepancies observed in the rate of prescription and the time of results.
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