The European Society for Medical Oncology (ESMO ) is a leading European professional organization for medical oncology and is considered the reference society for oncology education and information. Comprised of more than 13,000 oncology professionals from over 130 countries, ESMO is a home for all oncology stakeholders, and connects professionals with diverse expertise and experience.
ESMO Clinical Practice Guidelines (CPG) provides a set of recommendations for the best standards of cancer care, based on the findings of evidence-based medicine. An update to their Consensus Guidelines for the Management of Patients with Metastatic Colorectal Cancer (mCRC) was recently published in the July issue of the Annals_of_Oncology , ESMO’s official scientific journal. These ESMO Consensus Guidelines aim to reflect the diagnostic, therapeutic and strategic improvements which have contributed to the current treatment approaches and to provide guidance for the comprehensive management of patients with mCRC going forward (1).
In December 2014, ESMO convened an international consensus panel of experts which focused on three subgroups, one of which was molecular pathology and biomarkers. Within this subgroup, the recommendations on the following topics were included: selection of specimens for biomarker testing, RAS testing, BRAF testing, MSI testing, biomarkers of chemotherapy sensitivity, and emerging biomarkers not recommended for routine patient management outside of a clinical trial setting. The subsequent recommendations are based on significant new clinical trial evidence and an advanced understanding of the role and impact of molecular selection (2, 3). One of the major innovative additions to the guidelines is the development of a detailed therapeutic algorithm that takes into account the patient’s condition and fitness, therapeutic goals such as tumor shrinkage or slowing disease progression, and molecular markers. Recommendations made by the consensus panel include RAS and BRAF mutation testing at diagnosis for all patients with metastatic colorectal cancer.
Within the recommendations for biomarkers of chemotherapy sensitivity, a new predictive biomarker is now included in the guidelines. The new biomarker involves polymorphisms in a gene in the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1). UGT1A1 is responsible for bilirubin glucuronidation as well as glucuronidation of SN-38, the active metabolite of the chemotherapy drug irinotecan, used to treat bowel cancer. The ESMO guidelines state that UGT1A1 gene polymorphisms are predictive of severe irinotecan-related side-effects, including diarrhea, neutropaenia and vomiting. It is recommended that UGT1A1 phenotyping be carried out in patients with a suspicion of UGT1A1 deficiency as reflected by low conjugated bilirubin, as well as in patients being given an irinotecan dose of >180 mg/m2 per administration.
In 2005, the US FDA approved a genetic test for UGT1A1*28 and altered the irinotecan package insert to include toxicity and dosing warnings relating to the UGT1A1*28 allele (4). In 2010 the importance of UGT1A1 as a predictive biomarker for irinotecan toxicity was further verified in a review article on irinotecan pharmacogenomics by Marsh and Hopkins (5). Due to the growing clinical evidence for UGT1A1 as an important predictive marker for chemotherapy response, the demand for UGT1A1 testing in pathology labs began to grow. To make it easier for labs to meet the demand for increased UGT1A1 testing, QIAGEN developed the therascreen_UGT1A1_Pyro_Kit, an in vitro diagnostic (IVD) kit available in Europe and other countries across the globe outside of North America. This UGT1A1 kit is used for easy genotyping of allele variants *28 and *6 of the human UGT1A1 gene. A research use only version is also available for researchers worldwide. The historical evidence for UGT1A1 as a predictive biomarker for irinotecan toxicity, along with the new ESMO recommendations for UGT1A1 patient phenotyping, should support UGT1A1 testing on a more routine basis. The availability of QIAGEN’s therascreen UGTA1A1 IVD kit enables easy interpretation of complex results, should make this test easier for labs to implement.
QIAGEN has a leading portfolio of Sample to Insight technologies and solutions for biomarker_testing_in_colorectal_cancer, which include therascreen’s IVD pyrosequencing kits for reliable detection of mutations in RAS and BRAF, approved for use in Europe only. QIAGEN’s FDA-approved therascreen_KRAS_RGQ_PCR_Kit is available in the US and Canada, while its CE-IVD version available in Europe is also approved for NSCLC patient testing.
QIAGEN’s Personalized Healthcare and Oncology solutions offer many benefits, including convenient biomarker testing, reliable, efficient and cost effective workflows, and secure systems with experienced services and support. Find out more about QIAGEN’s oncology companion diagnostics solutions in the US and those available in Europe.
- 1. Van Cutsem, E. et al. (2016) ESMO Consensus Guidelines for the Management of Patients with Metastatic Colorectal Cancer. Annals of Oncology 8:1386-422; doi:10.1093/annonc/mdw235. (Link)
- 2. European Society for Medical Oncology. “New consensus guidelines on the management of metastatic colorectal cancer: Guidelines reflect personalized treatment approach.” ScienceDaily. 6 July 2016. (Link)
- 3. ESMO Releases New Consensus Guidelines on the Management of Metastatic Colorectal Cancer. The ASCO post 7/8/2016. (Link)
- 4. Staessen J.A. et al. (2005) FDA clears Third Wave pharmacogenetic test. Pharmacogenomics 6(7):671–672; doi:10.2217/146224220.127.116.111 (Link)
- 5. Marsh S. and Hoskins J.M. (2010) Irinotecan pharmacogenomics. Pharmacogenomics 11(7):1003-10; doi: 10.2217/pgs.10.95. (Link)