Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial
| العنوان: | Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial |
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| المؤلفون: | Catherine Jane Bale, Rachel Butler, S Waters, Angela C. Casbard, Sarah Moon, Andrew Foxley, Ramachandran Venkitaraman, Catrin Cox, Johnathan Joffe, Tracie-Ann Madden, Fouad S Alchami, Margherita Carucci, Robert H. Jones, Chris Twelves, Pavel Bezecny, Sacha J Howell |
| المصدر: | Jones, R, Casbard, A, Carucci, M, Cox, C, Butler, R, Alchami, F, Madden, T-A, Bale, C, Bezecny, P, Joffe, J, Moon, S, Twelves, C, Venkitaraman, R, Waters, S, Foxley, A & Howell, S 2020, ' Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION) : a multicentre, randomised, controlled, phase 2 trial ', The Lancet Oncology, vol. 21, no. 3, pp. 345-357 . https://doi.org/10.1016/S1470-2045(19)30817-4 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Fulvestrant/administration & dosage, Drug Resistance, Neoplasm/drug effects, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Neoplasm Metastasis, Fulvestrant, Aged, 80 and over, Manchester Cancer Research Centre, Aromatase Inhibitors, Hazard ratio, Carcinoma, Ductal, Breast, Middle Aged, Prognosis, Survival Rate, Neoplasm Recurrence, Local/drug therapy, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Receptors, Estrogen/metabolism, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, Breast Neoplasms, Carcinoma, Lobular/drug therapy, Placebo, 03 medical and health sciences, Breast Neoplasms/drug therapy, Double-Blind Method, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Pyrroles, Pyrimidines/administration & dosage, Survival rate, Aged, Salvage Therapy, Aromatase Inhibitors/pharmacology, Intention-to-treat analysis, Aromatase inhibitor, business.industry, Pyrroles/administration & dosage, ResearchInstitutes_Networks_Beacons/mcrc, Carcinoma, Lobular, 030104 developmental biology, Pyrimidines, Carcinoma, Ductal, Breast/drug therapy, Drug Resistance, Neoplasm, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Neoplasm Recurrence, Local, business, Follow-Up Studies |
| الوصف: | Background Capivasertib (AZD5363) is a potent selective oral inhibitor of all three isoforms of, the serine/threonine kinase, Akt. Akt inhibitors are anticipated to have maximal efficacy in combination with chemotherapy, targeted, or anti-hormonal drugs. The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progression-free survival in patients with aromatase inhibitor resistant advanced breast cancer.Methods In this randomised, phase 2, double-blind, placebo-controlled trial, postmenopausal women aged at least18 years with an Eastern Cooperative Oncology Group performance status of 0–2 and oestrogen receptor-positive,HER2-negative, metastatic or locally advanced inoperable breast cancer who had relapsed or progressed on an aromatase inhibitor were recruited from 19 UK centres. Enrolled participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a loading dose onday 15 of cycle 1) with either capivasertib 400 mg or matching placebo, orally twice daily on an intermittent weekly schedule of 4 days on and 3 days off (starting on cycle 1 day 15) until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent. Treatment allocation was done using an interactive web-response system using a minimisation method (with a 20% random element) and the following stratification factors: measurable or non-measurable disease, primary or secondary aromatase inhibitor resistance, PIK3CA status, and PTEN status. The primary endpoint was progression-free survival with a one-sided alpha of 0·20. Analyses were done by intention to treat. All recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, number NCT01992952.Findings Between March 16, 2015, and March 6, 2018, 183 patients were screened for eligibility, of whom 140 (76%) were eligible and were randomly assigned to receive fulvestrant plus capivasertib (n=69) or fulvestrant plus placebo (n=71). Median follow-up for progression-free survival was 4·9 months (IQR 1·6–11·6). At the time of primary analysis for progression-free survival, 112 progression-free survival events had occurred, 49 (71%) in 69 patients in the capivasertib group compared with 63 (89%) of 71 in the placebo group. Medianprogression-free survival was 10·3 months (95% CI 5·0–13·2) in the capivasertib group versus 4·8 months (95% CI 3·1–7·7) in the placebo group, giving an unadjusted hazard ratio (HR) of 0·58 (95% CI 0·39–0·84) in favour of thecapivasertib group (two-sided p=0·0044; one-sided log rank test p-0·0018). The most common grade 3–4 adverse events were hypertension (22 [32%] of 69 patients in the capivasertib group vs 17 [24%] of 71 in the placebo group), diarrhoea (10 [14%] vs 3 [4%]), rash (14 [20%] vs 0), infection (4 [5%] vs 2 [3%]), and fatigue (1 [1%] vs 3 [4%]). Serious adverse reactions occurred only in the capivasertib group, and were acute kidney injury (2), diarrhoea (3), rash (2), hyperglycaemia (1), loss of consciousness (1), sepsis (1), and vomiting (1). One death, due to atypical pulmonary infection, was assessed as possibly related to capivasertib treatment. One further death in the capivasertib group had an unknown cause; all remaining deaths in both groups were disease related.Interpretation Progression-free survival was significantly longer in participants who received capivasertib than in those who received placebo. The combination of capivasertib and fulvestrant warrants further investigation in phase 3 trials. |
| تدمد: | 1474-5488 1470-2045 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::be3e1775f72f2c39bba92c189237cd97 https://pubmed.ncbi.nlm.nih.gov/32359499 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....be3e1775f72f2c39bba92c189237cd97 |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 14745488 14702045 |
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