Sie sind bereits registriert?
Loggen Sie sich mit Ihrem Universimed-Benutzerkonto ein:
Sie sind noch nicht registriert?
Registrieren Sie sich jetzt kostenlos auf universimed.com und erhalten Sie Zugang zu allen Artikeln, bewerten Sie Inhalte und speichern Sie interessante Beiträge in Ihrem persönlichen Bereich zum späteren Lesen. Ihre Registrierung ist für alle Unversimed-Portale gültig. (inkl. allgemeineplus.at & med-Diplom.at)
Adagrasib Shows Promise in Colorectal Cancer with KRAS G12C Mutation
KRAS mutations are ubiquitous across a broad spectrum of malignancies. Adagrasib is a novel oral agent that irreversibly binds to mutant KRAS G12C protein in its inactive, GDP-bound state. Preclinical data indicate that epidermal growth factor receptor (EGFR) inhibitors may potentiate the activity of adagrasib.
Investigators report results of a phase 1–2, industry-sponsored, nonrandomized, open-label trial of adagrasib in heavily pretreated patients with metastatic colorectal cancer harboring a KRAS G12C mutation. Patients were treated either with adagrasib alone or combined with the EGFR inhibitor cetuximab. Of the 76 patients treated, most (63%) had received three or more prior regimens, most (63%) had liver metastases, and most (68%) had p53 mutations.
Of 43 evaluable patients treated with single-agent adagrasib, 23% responded. During a median follow-up of 20.1 months, median duration of response was 4.3 months, progression-free survival (PFS) was 5.6 months, and overall survival (OS) was 19.8 months. Of 28 evaluable patients treated with adagrasib plus cetuximab, 46% responded. During a median follow-up of 17.5 months, median duration of response was 7.6 months, PFS was 6.9 months, and OS was 13.4 months. Grade 3/4 treatment-related adverse events occurred in 34% of patients treated with adagrasib alone, including anemia and diarrhea, and in 16% of those treated with combination therapy, ultimately leading to cetuximab discontinuation in 16%.
KRAS G12C has emerged as a targetable mutation in colorectal cancer with a significant signal of activity for adagrasib and a potentially higher chance of response with the addition of cetuximab. Further study of this agent and combination are warranted.
Yaeger R et al.
Title: Adagrasib with or without cetuximab in colorectal cancer with mutated KRAS G12C.
Source: N Engl J Med 2023 Jan 5; [e-pub]. (Abstract/FREE Full Text)