The KRAS mutation detection within the initial management of patients with metastatic colorectal cancer: A status report in France in 2011

Lièvre, Astrid; Artru, Pascal; Guiu, Michel; Laurent‐Puig, Pierre; Merlin, Jean‐Louis; Sabourin, Jean‐Christophe; Viguier, Jérôme; Bastie, Anne; Seronde, Audrey; Ducreux, Michel

doi:10.1016/j.ejca.2013.02.016

Cited by 18 publications

(20 citation statements)

References 38 publications

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“…Similar data were obtained in a US Community Setting 102. In a more recent observational French study, 433/583 (81.1%) mCRC patients underwent KRAS testing 103. It was mainly requested by oncologists (n=195; 45.5%) and gastroenterologists (n=133; 31.0%) 103…”

Section: Practicesupporting

confidence: 69%

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs and beyond

et al. 2013

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Metastatic colorectal cancer harbouring a mutation in codon 12 or 13 of the KRAS gene does not benefit from therapy with antibodies targeting the epidermal growth factor receptor (EGFR). The implementation of community KRAS testing is generating a rapid flow of new data that have implications for the pathologist and testing guidelines besides the physician. Therefore, it seems timely to draw together the threads of this large body of information in order that pathologists can be knowledgeable partners in the multidisciplinary process of targeted cancer therapy and to help refine current testing guidelines. This review addresses (1) the most relevant methodological and technical aspects of KRAS testing in terms of sample site (primary/metastatic), test specimens (resection/biopsy/cytology) and the diverse molecular methods available; (2) the issues related to daily practice, namely, the timing of the test, its turnaround time and the quality control procedures; and (3) the evidence related to the relationship between KRAS genetic intratumoural heterogeneity, clinical sensitivity of mutational detection tools and anti-EGFR treatment outcome. Hopefully, in the near future, elucidation of the potential of biomarker panels and of the mechanisms underlying primary and acquired resistance to anti-EGFR therapy will refine even further personalised treatment regimens for patients with metastatic colorectal cancer.

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Section: Practicesupporting

confidence: 69%

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs and beyond

et al. 2013

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“…The median overall TAT for the four test sites that contributed these data was 9, 14, 16 and 22 days, while the average was 11, 17, 23 and 25 days, respectively. These results compare to a mean overall TAT of 24 days for 160 French testing centers . Data were not provided by five of the Australian test sites and hence we cannot reach firm conclusions regarding TAT in this country compared with benchmark standards from overseas.…”

Section: Discussionmentioning

confidence: 65%

“…Although too numerous to list here, the great majority of publications on KRAS mutation in CRC have reported frequencies that lie within the range of 34–42%. For example, two recent French studies of 674 and 356 cases of mCRC found KRAS mutation frequencies of 38.0% and 37.4%, respectively . Frequencies that lie outside the range of 34–42% may therefore not be accurate.…”

Section: Discussionmentioning

confidence: 99%

KRAS mutation testing of metastatic colorectal cancer in Australia: Where are we at?

Scott

Fox

Desai

et al. 2014

Asia-Pac J Clncl Oncology

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The frequency of KRAS mutations in metastatic colorectal cancer reported by the major Australian test sites is very similar to that reported by other large overseas studies. More widespread introduction of routine testing at the time of initial diagnosis should eliminate the long turnaround times currently being experienced in a significant proportion of cases. Future expansion of testing to include other KRAS and NRAS mutation hotspots may spur the introduction of next-generation sequencing platforms.

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“…Panelists agree that in patients with metachronous metastases this may be undoubtedly realized by anticipating KRAS test before the onset of metastatic disease, meeting the need of improving decision making in clinical practice, as it has been recently underlined [10]. In the opinion of most experts the right time for KRAS test is after radical resection of CRC.…”

Section: Discussionmentioning

confidence: 97%

KRAS Early Testing: Consensus Initiative and Cost-Effectiveness Evaluation for Metastatic Colorectal Patients in an Italian Setting

Barone

Pinto

Normanno³

et al. 2014

PLoS ONE

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KRAS testing is relevant for the choice of the most appropriate first-line therapy of metastatic colorectal cancer (CRC). Strategies for preventing unequal access to the test should be implemented, but their relevance in the practice is related to economic sustainability. The study adopted the Delphi technique to reach a consensus on several topics. Issues related to execution of KRAS testing were identified by an expert’s board and proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The emerging proposal was evaluated by decision analyses models employed by technology assessment agencies in order to assess cost-effectiveness. Alternative therapeutic strategies included most commonly used chemotherapy regimens alone or in combination with cetuximab or bevacizumab. The survey indicated that time interval for obtaining KRAS test should not exceed 15 days, 10 days being an optimal interval. To assure the access to proper treatment, a useful strategy should be to anticipate the test after radical resection in patients at high risk of relapse. Early KRAS testing in high risk CRC patients generates incremental cost-effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY) gained. In extensive sensitivity analyses ICER’s were always below 15,000 Euro per QALY gained, far within the threshold of 60,000 Euro/QALY gained accepted by regulatory institutions in Italy. In metastatic CRC a time interval higher than 15 days for result of KRAS testing limits access to therapeutic choices. Anticipating KRAS testing before the onset of metastatic disease in patients at high risk does not affect the sustainability and cost-effectiveness profile of cetuximab in first-line mCRC. Early KRAS testing may prevent this inequality in high-risk patients, whether they develop metastases, and is a cost-effective strategy. Based on these results, present joined recommendations of Italian societies of Oncology and Pathology should be updated including early KRAS testing.

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The KRAS mutation detection within the initial management of patients with metastatic colorectal cancer: A status report in France in 2011

Cited by 18 publications

References 38 publications

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs and beyond

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs and beyond

KRAS mutation testing of metastatic colorectal cancer in Australia: Where are we at?

KRAS Early Testing: Consensus Initiative and Cost-Effectiveness Evaluation for Metastatic Colorectal Patients in an Italian Setting

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