Adding capivasertib to fulvestrant improves the progression-free survival (PFS) in postmenopausal women with oestrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer resistant to aromatase inhibitors, concluded Jones et al. (2020) in Lancet Oncology.¹Jones RH, et al. Lancet Oncol. 2020 pii: S1470-2045(19)30817-4.

“FAKTION met its primary outcome in showing that the combination of fulvestrant and capivasertib is tolerable and produces a significant improvement in progression-free survival for participants with advanced oestrogen receptor-positive HER2-negative breast cancer who have previously progressed on an aromatase inhibitor,” first author Dr Jones, and his colleagues wrote in The Lancet Oncology.¹Jones RH, et al. Lancet Oncol. 2020 pii: S1470-2045(19)30817-4..

FAKTION Trial

The double-blind phase II FAKTION trial (NCT01992952) randomised 140 patients 1:1 to either capivasertib plus fulvestrant (n=69) or placebo plus fulvestrant (n=71).¹Jones RH, et al. Lancet Oncol. 2020 pii: S1470-2045(19)30817-4. Eligible patients included postmenopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer that had relapsed or progressed on — or within 12 months of — adjuvant aromatase inhibitor therapy in the metastatic setting. Patients previously treated with fulvestrant or inhibitors of the PI3K/AKT pathway, or those with clinically significant abnormalities of the glucose metabolism were excluded. The primary efficacy endpoint was PFS. Patients were stratified according to the PI3K/PTEN pathway alteration status.

Results

The median PFS was 10.3 months in the capivasertib plus fulvestrant group, and 4.8 months in the placebo group (HR=0.58; 95% CI, 0.39–0.84; two-sided p=0.0044; one-sided log-rank test p=0.0018) in favour of the capivasertib group.

Interestingly, the addition of the AKT-inhibitor capivasertib to fulvestrant did not show a pronounced efficacy in the subgroup of patients with alterations in the Pi3K/PTEN pathway; the median PFS measured 9.5 months in the capivasertib group and 5.2 months in the placebo group. The outcome in the patients without Pi3K/PTEN alterations was similar to the overall result; a median PFS of 10.3 months vs 4.8 months for capivasertib plus fulvestrant vs placebo plus fulvestrant, respectively.

Safety

The most common grade ≥3 adverse events included hypertension (32% vs 24%), diarrhoea (14% vs 4%), rash (20% vs 0), and infection (6% vs 3%) in patients receiving capivasertib and fulvestrant vs those receiving placebo and fulvestrant, respectively. Serious adverse reactions only occurred in the capivasertib group, and included acute kidney injury (n=2), diarrhoea (n=3), rash (n=2), hyperglycaemia (n=1), loss of consciousness (n=1), sepsis (n=1), and vomiting (n=1). There was one death of unknown cause in the capivasertib group.

Reference

1. Jones RH, et al. Lancet Oncol. 2020 pii: S1470-2045(19)30817-4.