BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population
| العنوان: | BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population |
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| المؤلفون: | E. De Bruin, M.P. Sablin, S.Y.A. Cheung, Barry R. Davies, Michele Moschetta, E. Outhwaite, Marie Cullberg, Kenji Tamura, J. Lindemann, Claire Corcoran, E. Alarcón, Martin Pass, Andrew Foxley, Jose Alejandro Perez-Fidalgo, Y.A. López Chuken, M. Philco, Gaia Schiavon, A. Gómez Villanueva, Rhiannon Maudsley, Nicholas C. Turner, Mafalda Oliveira, Anne C Armstrong, Paul Rugman |
| المساهمون: | 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, Hospital Universitari Vall d'Hebron |
| المصدر: | Scientia Recercat. Dipósit de la Recerca de Catalunya instname Annals of oncology : official journal of the European Society for Medical Oncology r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA Annals of Oncology Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| بيانات النشر: | Oxford University Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Estrogen receptor, aminoácidos, péptidos y proteínas::proteínas::receptores citoplásmicos y nucleares::receptores de esteroides::receptores de estrógenos [COMPUESTOS QUÍMICOS Y DROGAS], Other subheadings::Other subheadings::/drug therapy [Other subheadings], AKT inhibitor, ER+, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Breast Tumors, Neoplasm Metastasis, education.field_of_study, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES], Hematology, Metastatic breast cancer, Survival Rate, Receptors, Estrogen, Paclitaxel, Tolerability, 030220 oncology & carcinogenesis, Female, metastatic breast cancer, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, Population, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Breast Neoplasms, capivasertib, 03 medical and health sciences, Breast cancer, Double-Blind Method, Metàstasi, Internal medicine, Biomarkers, Tumor, medicine, Humans, Pyrroles, education, Survival rate, neoplasms, business.industry, Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [CHEMICALS AND DRUGS], Cancer, HER2−, Original Articles, PIK3CA, medicine.disease, Pyrimidines, 030104 developmental biology, chemistry, Estrògens - Receptors, neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES], Mutation, Mama - Càncer - Tractament, Neoplasm Recurrence, Local, business, Proto-Oncogene Proteins c-akt |
| الوصف: | 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). |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1569-8041 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e859acd761a1223f94f5a89e6ed174abTest https://hdl.handle.net/11351/5759Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e859acd761a1223f94f5a89e6ed174ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15698041 |
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