fulvestrant + lucitanib

This is a combination therapy consisting of fulvestrant, a selective estrogen receptor degrader (SERD), and lucitanib, an oral small molecule tyrosine kinase inhibitor targeting fibroblast growth factor receptors (FGFR1–3), vascular endothelial growth factor receptors (VEGFR1–3), and platelet-derived growth factor receptors (PDGFRα/β). The combination was investigated in postmenopausal women with estrogen receptor-positive, HER2-negative metastatic breast cancer, including those with or without FGFR1 amplification. Fulvestrant acts by binding to and accelerating the degradation of the estrogen receptor, thereby inhibiting estrogen signaling. Lucitanib inhibits angiogenesis and tumor cell proliferation by blocking multiple tyrosine kinase pathways involved in tumor progression. The rationale for this combination was to overcome resistance to endocrine therapy via FGFR pathway inhibition; however, clinical studies did not confirm reversal of resistance in preclinical models. The regimen required close monitoring due to significant toxicities such as hypertension and asthenia[1][5].