Preclinical Rationale, Clinical Efficacy, and Safety of the Selective AKT Kinase Inhibitor Capivasertib in Metastatic Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Carcinoma: A Practical Narrative Review.
Most patients with advanced/metastatic hormone receptor-positive, HER2-negative breast cancer receive first-line therapy with cycline-dependent kinase 4/6 inhibitors plus endocrine therapy. Almost universally, these patients eventually progress due to the emergence of resistant cancer clones. Targeting the PIK3CA/AKT1/PTEN pathway is a way of overcoming resistance. Recently, the oral, selective AKT kinase inhibitor capivasertib has been approved for the treatment of estrogen receptor-positive/human HER2-growth factor receptor-2 advanced BC with alterations in PIK3CA/AKT1/PTEN, in combination with fulvestrant after progression on endocrine therapy. We performed a narrative review to recapitulate the available evidence about capivasertib in the management of advanced hormone receptor-positive, HER2-negative breast cancer, focusing on studies that address preclinical rationale, pharmacology, and clinically relevant problems.
Authors
Valerio Valerio, Sambataro Sambataro, Martorana Martorana, Greco Greco, Mesi Mesi, Gebbia Gebbia, Vigneri Vigneri, Scandurra Scandurra
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