In a phase 3, randomized, double-blind trial of patients with hormone receptor–positive advanced breast cancer, progression-free survival was significantly longer with the AKT inhibitor capivasertib plus fulvestrant than with fulvestrant alone, researchers report. Disease had progressed during or after previous aromatase inhibitor therapy with or without a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor in all participants.
The CAPItello-291 trial randomly assigned participants to receive capivasertib plus fulvestrant or placebo plus fulvestrant. Based on dual primary endpoints of investigator-assessed progression-free survival in the overall population and among patients with AKT pathway–altered (PIK3CA, AKT1, or PTEN) tumors, the study showed the following: “Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib–fulvestrant group, as compared with 3.6 months in the placebo–fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P <0.001). In the AKT pathway–altered population, the median progression-free survival was 7.3 months in the capivasertib–fulvestrant group, as compared with 3.1 months in the placebo–fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P <0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib–fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo–fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo.”