TY - JOUR
TI - “The emerging role of capivasertib in breast cancer”
AU - Andrikopoulou, A.
AU - Chatzinikolaou, S.
AU - Panourgias, E.
AU - Kaparelou, M.
AU - Liontos, M.
AU - Dimopoulos, M.-A.
AU - Zagouri, F.
JO - Gastric and Breast Cancer
PY - 2022
VL - 63
TODO - null
SP - 157-167
PB - Churchill Livingstone
SN - null
TODO - 10.1016/j.breast.2022.03.018
TODO - 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
TODO - 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
ER -