Capivasertib: A Novel AKT Inhibitor Approved for Hormone-Receptor-Positive, HER-2-Negative Metastatic Breast Cancer.
Ann Pharmacother
; : 10600280241241531, 2024 Apr 02.
Article
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| MEDLINE
| ID: mdl-38566315
ABSTRACT
OBJECTIVE:
To review the pharmacology, efficacy, and safety of capivasertib for the treatment of adults with hormone receptor-positive, HER2-negative (HR+/HER2-) locally advanced or metastatic breast cancer with 1 or more PIK3CA/AKT1/PTEN alterations. DATA SOURCES A literature search was conducted using PubMed and MEDLINE databases, published abstracts, and studies from ClinicalTrials.gov between 2003 and February 2024. Keywords included capivasertib, AZD5363, PI3K/AKT/mTOR pathway, and breast cancer. DATA EXTRACTION All applicable publications, package inserts, meeting abstracts, and clinical trials with capivasertib were reviewed. DATASYNTHESIS:
Capivasertib is a first-in-class inhibitor of 3 isoforms of AKT (AKT-1, AKT-2, and AKT-3) which is an essential component in the PI3K/AKT/mTOR signaling pathway involved in oncogenesis. In the phase III CAPItello-291 trial, capivasertib in combination with fulvestrant (C+F) demonstrated improved progression-free survival (PFS) (7.3 vs 3.1 months) compared with placebo-fulvestrant (P+F) cohort in AKT-altered pathway patients who had progressed through prior aromatase inhibitor. The most common adverse reactions of any grade reported in the C+F group were diarrhea, cutaneous skin reactions, nausea, fatigue, and vomiting. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS HR+/HER2- advanced breast cancer patients experience progression following endocrine therapies and cyclin-dependent kinase (CDK) 4/6 inhibitors. Capivasertib is a viable treatment option for patients with PIK3CA/AKT1/PTEN activating mutations following progression on endocrine-based regimens in the metastatic setting or recurrence within 12 months of completing adjuvant therapy.CONCLUSION:
Integration of capivasertib into clinical practice is ongoing; intermittent dosing and favorable toxicity are attractive for future novel combination prospective trials.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Ann Pharmacother
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos