The addition of the novel, pan-AKT kinase inhibitor capivasertib to fulvestrant significantly prolongs the progression-free survival (PFS) in patients with hormone receptor-positive, HER2-negative breast cancer. These findings were recently presented at the San Antonio Breast Cancer Symposium.
A phase III randomised CAPItello-291 trial was conducted to investigate the efficacy and safety of capivasertib for breast cancer patients.
The randomized, phase III CAPItello-291 trial enrolled 708 patients with histologically confirmed hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. All the participants experienced disease progression or recurrence during or after aromatase inhibitor therapy, with or without a cyclin-dependent kinase 4/6 inhibitor. The enrolled participants were randomly (1:1) divided to receive fulvestrant and either capivasertib (n = 355) or placebo (n = 353). The study’s primary endpoint was the progression-free survival (PFS) in overall population and subgroup with altered AKT-pathway. The secondary points were overall survival (OS) and objective response rate (ORR).
The researchers reported an extended PFS of 7.2 months in the capivasertib group than placebo (3.6 months, HR = 0.6; 95% CI, 0.51-0.71). Furthermore, a higher ORR was seen in the capivasertib arm compared to the control arm (22.9% vs. 12.2%).
Among the subgroup with AKT mutations (41%) too, an increased PFS (7.3 months vs 3.1 months; adjusted HR = 0.5; 95% CI, 0.38-0.65) and ORR (28.8% vs. 9.7%) was observed with administration of capivasertib. The remaining patients with no alteration in the AKT pathway also had longer PFS (7.2 months vs 3.7 months; HR = 0.7; 95% CI, 0.56-0.88) with capivasertib.
The AKT inhibitor capivasertib had a safe and manageable safety profile. The common grade 3 or higher adverse events included rash (12.1%), diarrhoea (9.3%) and hyperglycemia (2.3%). Further, more patients treated with capivasertib discontinued treatment than with placebo (13% vs 2.3%).
The results of the CAPItello-219 trial demonstrate the clinical efficacy and safety of capivasertib. Its combination with fulvestrant has the potential to become a treatment option for hormone receptor-positive advanced breast cancer patients.