Sistema de Salut de Catalunya
Turner, N. C.
Alarcón, E.
Armstrong, A. C.
Philco, M.
López Chuken, Y. A.
Sablin, Marie-Paule
Antunes de Melo Oliveira, Ana Mafalda
Institut Català de la Salut
[Turner NC] Breast Unit, The Royal Marsden NHS Foundation Trust, London, UK. Breast Cancer Now Research Centre, The Institute of Cancer Research, London, UK. [Alarcón E] Clinical Oncology Department, British American Hospital, Lima, Peru. [Armstrong AC] Department of Medical Oncology, Christie Hospital NHS Foundation Trust and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. [Philco M] Peruvian Institute of Oncology Radiotherapy, Lima, Peru. [López Chuken YA] University Hospital, Monterrey, Mexico. [Sablin MP] Department of Drug Development and Innovation (D3i), Curie Institute, Paris, France. [Oliveira, M] Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2021-03-16T09:36:56Z
2021-03-16T09:36:56Z
2019-05-01
Inhibidor de l'AKT; PIK3CA; Capivasertib
Inhibidor de AKT; PIK3CA; Capivasertib
AKT inhibitor; PIK3CA; Capivasertib
Background BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1–3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer, and in a phosphoinositide 3-kinase, catalytic, alpha polypeptide mutation sub-population (PIK3CA+). Patients and methods BEECH consisted of an open-label, phase Ib safety run-in (part A) in 38 patients with advanced breast cancer, and a randomised, placebo-controlled, double-blind, phase II expansion (part B) in 110 women with ER+/HER2− metastatic breast cancer. In part A, patients received paclitaxel 90 mg/m2 (days 1, 8 and 15 of a 28-day cycle) with capivasertib taken twice daily (b.i.d.) at two intermittent ascending dosing schedules. In part B, patients were randomly assigned, stratified by PIK3CA mutation status, to receive paclitaxel with either capivasertib or placebo. The primary end point for part A was safety to recommend a dose and schedule for part B; primary end points for part B were progression-free survival (PFS) in the overall and PIK3CA+ sub-population. Results Capivasertib was well tolerated, with a 400 mg b.i.d. 4 days on/3 days off treatment schedule selected in part A. In part B, median PFS in the overall population was 10.9 months with capivasertib versus 8.4 months with placebo [hazard ratio (HR) 0.80; P = 0.308]. In the PIK3CA+ sub-population, median PFS was 10.9 months with capivasertib versus 10.8 months with placebo (HR 1.11; P = 0.760). Based on the Common Terminology Criteria for Adverse Event v4.0, the most common grade ≥3 adverse events in the capivasertib group were diarrhoea, hyperglycaemia, neutropoenia and maculopapular rash. Dose intensity of paclitaxel was similar in both groups. Conclusions Capivasertib had no apparent impact on the tolerability and dose intensity of paclitaxel. Adding capivasertib to weekly paclitaxel did not prolong PFS in the overall population or PIK3CA+ sub-population of ER+/HER2− advanced/metastatic breast cancer patients.
This study was supported by AstraZeneca (no grant number applies).
English
Estrògens - Receptors; Metàstasi; Mama - Càncer - Tractament; DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen; ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::receptores citoplásmicos y nucleares::receptores de esteroides::receptores de estrógenos
Oxford University Press
Annals of Oncology;30(5)
https://www.annalsofoncology.org/article/S0923-7534(19)31171-8/fulltext
Attribution-NonCommercial 4.0 International
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
Articles científics - HVH [3370]
