The US FDA has approved vepdegestrant for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced or metastatic breast cancer, with disease progression following at least one line of endocrine therapy. Vepdegestrant is a heterobifunctional protein degrader that binds to ER and the E3 ligase cereblon, leading to proteasome-mediated degradation of the receptor and a reduction in ER protein levels in breast cancer cells.
In vitro, it inhibits proliferation of ER-dependent breast cancer cell lines, while in vivo studies have demonstrated antitumor activity against both wild-type and ESR1-mutant breast cancer models. Clinical evidence In a clinical trial involving 270 patients with ESR1 mutations, vepdegestrant reduced the risk of disease progression by 43% compared with fulvestrant.…
