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Therapeutic use and handling of anti-EGFR antibodies in colorectal cancers


Hépato-Gastro. Volume 15, 18-22, Numéro spécial : Actualité 2008 dans le cancer colorectal, Mini-revue

Résumé   Article gratuit  

Author(s) : Thierry André

Summary : The last decade has witnessed a major improvement in the management of metastatic colorectal cancers. Median survival time increased from 12 months in 1995, with 5FU and folinic acid treatment, to 25-30 months nowadays due to a larger choice of drugs (chemotherapeutic agents and targeted therapies) and optimization of medico-surgical strategies. Unlike anti-angiogenic agents, anti-EGFR antibodies have initially been marketed for third-line use. They increase the response rate and progression free survival (PFS), particularly when they are associated with irinotecan (for cetuximab). Compared to best supportive care, they slightly improve global survival (cetuximab) and progression free survival (panitumumab). Trials assessing cetuximab in first- or second-line therapies have also shown a significant but modest improvement of PFS. These studies open the way for their use in the early phases of the disease, but it remains to be shown whether this is to be preferred to their use in third-line treatments. The issue of their optimal use in the therapeutic strategy remains unresolved. However, the benefit of these molecules is not the same for each patient. It is now known that KRAS mutations in tumor cells, which are found in 40% of colorectal cancers, are associated with lack of response to anti-EGFR antibodies. Panitumumab is the first treatment that has included this information in the instructions for use of its drug approval, even though this test is not yet commercialized. In light of this new knowledge, it is the whole anti-EGFR treatment strategy that has to be reassessed, in particular their use in first- and second-line treatments and in patients with potentially resectable metastases.

Keywords : Colorectal cancer, anti-EGFR antibody, KRAS mutation, cetuximab, panitumumab

 

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