Sotorasib for Vascular Malformations Associated with <i>KRAS</i> G12C Mutation.

Abstract

<i>KRAS</i> gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such <i>KRAS</i>-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic <i>Kras</i> G12C mutation. We then administered sotorasib to two adult patients with severe <i>KRAS</i> G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with <i>KRAS</i> G12C-related vascular malformations. (Funded by the European Research Council and others.).