KRAS G12C inhibition in colorectal cancer

Mené dans 11 pays sur 62 patients atteints d'un cancer colorectal présentant la mutation G12C du gène KRAS, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité du sotorasib en monothérapie, après l'échec d'une chimiothérapie à base de fluoropyrimidine, d'oxaliplatine et d'irinotécan

Résumé en anglais

For years, patients with metastatic colorectal cancer were considered and treatedas a single biological entity. Since the association between activated RAS mutations and low efficacy of anti-epidermal growth factor receptor (EGFR) therapybecame evident, it has been recommended that all patients with metastatic colorectalcancer are routinely tested for RAS mutations. Mutations in RAS are one the most frequent oncogenic drivers in human cancers, with a frequency ofnearly 50% in patients with metastatic colorectal cancer dominated by mutations in KRAS codon 12, but KRASG12C is only present in 3% of patients with metastatic colorectal cancer. In metastatic colorectal cancer, RAS mutations indicate poor prognosis, but patients with KRASG12C might have an even shorter overall survival than those with non-KRASG12C mutations. Until recently, abnormal RAS proteins were regarded as undruggable. However, in 2013,a breakthrough reported the development of small molecules that selectively and irreversiblybind to KRASG12C, and so far, early results of phase 2 studies of the two KRASG12C inhibitors, sotorasib and adagrasib, have been reported