Τίτλος:
“The emerging role of capivasertib in breast cancer”
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Over 50% of breast tumors harbor alterations in one or more genes of the phosphatidylinositol 3-kinase (PI3K) pathway including PIK3CA mutations (31%), PTEN loss (34%), PTEN mutations (5%) and AKT1 mutations (3%). While PI3K and mTOR inhibitors are already approved in advanced breast cancer, AKT inhibitors have been recently developed as a new therapeutic approach. Capivasertib (AZD5363) is a novel, selective ATP-competitive pan-AKT kinase inhibitor that exerts similar activity against the three AKT isoforms, AKT1, AKT2, and AKT3. Preclinical studies demonstrated efficacy of capivasertib in breast cancer cell lines as a single agent or in combination with anti-HER2 agents and endocrine treatment, especially in tumors with PIK3CA or MTOR alterations. Phase I/II studies demonstrated greater efficacy when capivasertib was co-administered with paclitaxel, fulvestrant in hormone receptor (HR)-positive, HER2-negative breast cancer or olaparib. The recommended phase II dose of capivasertib as monotherapy was 480 mg bid on a 4-days-on, 3-days-off dosing schedule. Toxicity profile proved to be manageable with hyperglycemia (20–24%), diarrhea (14–17%) and maculopapular rash (11–16%) being the most common grade ≥3 adverse events. Ongoing Phase III trials of capivasertib in combination with fulvestrant (CAPItello-291), CDK4/6 inhibitor palbociclib (CAPItello-292) and paclitaxel (CAPItello- 290) will better clarify the therapeutic role of capivasertib in breast cancer. © 2022
Συγγραφείς:
Andrikopoulou, A.
Chatzinikolaou, S.
Panourgias, E.
Kaparelou, M.
Liontos, M.
Dimopoulos, M.-A.
Zagouri, F.
Περιοδικό:
Gastric and Breast Cancer
Εκδότης:
Churchill Livingstone
Λέξεις-κλειδιά:
capivasertib; fulvestrant; mammalian target of rapamycin; olaparib; paclitaxel; palbociclib; phosphatidylinositol 3 kinase; placebo; protein AKT1; protein AKT3; protein kinase B; protein kinase B beta; unclassified drug; antineoplastic agent; capivasertib; epidermal growth factor receptor 2; fulvestrant; paclitaxel; phosphatidylinositol 3 kinase; phosphatidylinositol 4,5 bisphosphate 3 kinase; protein kinase B; protein kinase inhibitor; pyrimidine derivative; pyrrole derivative, anemia; antineoplastic activity; breast cancer; breast cancer cell line; cancer hormone therapy; diarrhea; drug approval; drug efficacy; drug mechanism; drug metabolism; drug potentiation; drug safety; drug tolerability; drug withdrawal; endometrium cancer; enzyme inhibitor interaction; estrogen receptor positive breast cancer; fatigue; female genital tract cancer; hormone receptor-positive, HER2-negative breast cancer; human; hyperglycemia; infection; maculopapular rash; metastatic breast cancer; monotherapy; nausea; neuropathy; nonhuman; outcome assessment; ovary cancer; overall survival; pharmacodynamics; progression free survival; QT prolongation; rash; Review; risk benefit analysis; signal transduction; solid malignant neoplasm; stomatitis; survival time; treatment duration; triple negative breast cancer; vomiting; breast tumor; female; genetics; mutation; pathology, Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Female; Fulvestrant; Humans; Mutation; Paclitaxel; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyrroles; Receptor, ErbB-2
DOI:
10.1016/j.breast.2022.03.018
