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)
A Novel Agent for Previously Treated Patients with ER+/HER2− Advanced Breast Cancer
Numerous novel anti-estrogens are in development with activity against tumors that express ESR1 mutations, which occur under pressure of treatment and confer resistance to subsequent endocrine therapy. The selective estrogen receptor degrader (SERD) elacestrant is the only such agent FDA-approved for tumors with ESR1 mutations.
The industry-funded, phase 3 VERITAC-2 trial enrolled 624 adults with ER+/HER2− advanced or metastatic breast cancer (including 270 with ESR1 mutations) who had received one line of CDK 4/6 inhibitor plus endocrine therapy. Investigators randomized patients to receive the investigational proteolysis-targeting chimera (PROTAC) ER degrader vepdegestrant (200 mg orally once daily continuously) or fulvestrant (500 mg intramuscularly on days 1 and 15 in the first 28-day cycle; on day 1 in subsequent cycles).
During a median follow-up of approximately 7 months, median progression-free survival (PFS) was significantly longer with vepdegestrant than fulvestrant among patients with ESR1 mutations (5.0 vs. 2.1 months) but not among all patients (3.8 vs. 3.6 months). Grade 3 or higher adverse events occurred in 23% of the vepdegestrant group and 18% of the fulvestrant group.
Comment
Vepdegestrant is the first PROTAC agent showing benefit over standard-therapy fulvestrant, though the advantage was restricted to patients with ESR1-mutated tumors. PROTACs are unique as they structurally include a ligand for the protein of interest (ER) and a ligand for E3 ligase, resulting in ubiquitination of the ER and degradation by the proteosome. Vepdegestrant was very well tolerated, and longer follow-up may identify subsets of patients who benefit most. Several new endocrine agents have shown similar improvements in PFS over fulvestrant in patients with ESR1-mutated tumors. If more than one are approved for this indication, deciding which is best may depend on personal preference, toxicity, and ability to combine with other targeted agents.
Citation(s)
Author:
Campone M et al.
Title:
Vepdegestrant, a PROTAC estrogen receptor degrader, in advanced breast cancer.
Source:
N Engl J Med
2025
May
31; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
William J. Gradishar, MD