Jones RH, Casbard A, Carucci M, et al. - In the FAKTION trial, researchers investigated whether progression-free survival in patients with aromatase inhibitor-resistant advanced breast cancer could be improved via adding capivasertib (a potent selective oral inhibitor of all three isoforms of the serine/threonine kinase AKT) to fulvestrant. In this randomized, double-blind, placebo-controlled, phase 2 trial, they recruited 140 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 from 19 hospitals in the UK. The participants were administered 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). Outcomes revealed significantly longer progression-free survival in participants who were administered capivasertib vs those receiving placebo. The capivasertib group had a median progression-free survival of 10·3 months (95% CI 5·0–13·2) vs 4·8 months (3·1–7·7) in the placebo group. 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 (14% vs 4%), rash (20% vs 0), infection (6% vs 3%), and fatigue (1% vs 4%). Only the capivasertib group, patients experienced serious adverse reactions, comprising acute kidney injury (two), diarrhoea (three), rash (two), hyperglycaemia (one), loss of consciousness (one), sepsis (one), and vomiting (one). One death, due to atypical pulmonary infection, assessed as possibly related to capivasertib treatment, and one further death in the capivasertib group with an unknown cause were reported. In both groups, all remaining deaths (19 in the capivasertib group and 31 in the placebo group) were disease-related.