Capivasertib plus fulvestrant versus placebo plus fulvestrant in metastatic ER positive breast cancer (FAKTION): A randomised, double-blind, placebo-controlled, phase II trial


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Robert Jones1,Margherita Carucci2,Angela Casbard2,Rachel Butler3,Catherine Bale4,Fouad Alchami5,Pavel Bezecny6,Johnathan Joffe7,Sarah Moon8,Chris Twelves9,Ramachandran Venkitaraman10,Simon Waters1,Sacha Howell11
1Velindre University NHS Trust, Cardiff, UK,2Cardiff University, Cardiff, UK,3North Bristol NHS Trust, Bristol, UK,4Betsi Cadwaladr University Health Board, Bangor, UK,5Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK,6Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, UK,7Royal College of Physicians of London, London, UK,8University Hospitals of Morecambe Bay NHS Trust, Milnthorpe Cumbria, UK,9University of Leeds and St. James's Institute of Oncology, Leeds, UK,10The Ipswich Hospital NHS Trust, Ipswich, UK,11The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK

Abstract

Background

The PI3K/AKT signalling pathway is frequently activated in patients (pts) with estrogen receptor (ER) positive breast cancer (ER+BC) and has been implicated in endocrine therapy resistance. Capivasertib is a highly-selective, oral, small molecule AKT inhibitor. The FAKTION trial investigated addition of capivasertib to fulvestrant for postmenopausal women with ER+ and HER2 negative BC after relapse or disease progression on an aromatase inhibitor (AI).

Method

FAKTION is an investigator-led, double-blind, placebo-controlled, randomised phase II trial. Patients were recruited from 21 UK sites and randomly assigned (1:1) to fulvestrant 500mg with either capivasertib 400mg bd or placebo (4 days on/3 days off starting C1D15). Minimisation according to PIK3CA mutation and PTEN expression status, measurable/non-measurable disease, and primary/secondary endocrine resistance occurred. The primary endpoint was progression-free survival (PFS). The trial had 90% power to detect a hazard ratio of 0.65 at the one-sided 20% significance level. Secondary endpoints included overall survival (OS), objective response and clinical benefit rates, safety and the effect of PI3K/Akt pathway activation on PFS.

Results

140 pts were randomised to fulvestrant + capivasertib (n = 69) or fulvestrant + placebo (n = 71). In the Intention-to-treat analysis, after 112 events, median PFS was 10.3 months (m) for capivasertib compared to 4.8m for placebo (Hazard Ratio (HR) 0.57; 95% CI: 0.39 to 0.84; one-sided p = 0.0017; two-sided 0.0035). Median OS was 26.0m for capivasertib compared to 20.0m for placebo, with a survival difference starting to emerge after 12m (HR = 0.59; 95% CI: 0.34 to 1.05; two-sided p = 0.071). Toxicity data and subgroup analyses including relative capivasertib benefit by PI3K/Akt pathway alteration will be presented.

Conclusion

The trial met its primary endpoint. Addition of capivasertib to fulvestrant for patients with endocrine resistant advanced breast cancer resulted in significantly longer PFS and an improvement in OS. The FAKTION results warrant further investigation.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.