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

Abstract

Background Capivasertib (AZD5363) is a potent selective oral inhibitor of all three isoforms of the serine/threonine kinase AKT. The FAKTION trial investigated whether the addition of capivasertib to fulvestrant improved progressionfree survival in patients with aromatase inhibitor-resistant advanced breast cancer.Methods In this randomised, double-blind, placebo-controlled, phase 2 trial, postmenopausal women aged at least 18 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 hospitals in the UK. Enrolled participants were randomly assigned (1:1) to receive intramuscular fulvestrant 500 mg (day 1) every 28 days (plus a loading dose on day 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 minimisation 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. Recruitment is complete, and the trial is in follow-up. This trial is registered with ClinicalTrials.gov, number NCT01992952.

Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial

“… 22 , 23 Capivasertib plus fulvestrant might be efficacious in endocrine-resistant oestrogen receptor-positive breast cancer without mutation selection, as shown in the FAKTION trial. 24 It is not possible to robustly compare plasmaMATCH with FAKTION, as patients enrolled in plasmaMATCH had more previous lines of treatment, and AKT1 mutations were not assessed and would be few in number in FAKTION. 24 …”

Comprehensive molecular profiling of Taiwanese breast cancers revealed potential therapeutic targets: prevalence of actionable mutations among 380 targeted sequencing analyses

“…Loss or inactivation mutation of PTEN (ESCAT Tier IIA) is a crucial step during breast carcinogenesis as PTEN is a negative regulator of PI3K pathway; PTEN acts as a direct antagonist of PI3K through dephosphorylation of PIP3. PTEN loss results in AKT-mTOR signaling activation, and capivasertib (AZD5363), an AKT inhibitor, can suppress the aberrant pathway [30]. In current study, 23 breast cancers harbored PTEN mutations, and capivasertib combined with fulvestrant or chemotherapy might be a choice of refractory diseases depending on hormone receptor status.…”

Comparison of Endocrine Therapies in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Network Meta-Analysis

“…After screening the titles and abstracts, 124 remaining records were considered to be eligible for a full text review. Ultimately, 35 articles were selected which met all the inclusion criteria, giving a total of 12,285 patients involved in this network meta-analysis, as shown in [ 7 8 12 13 14 15 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 ]. The search process based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique is shown in in Figure 1 [ 48 ].…”