Capivasertib

The phase III, randomized, double-blind CAPITELLO-291 trial (NCT04305496) enrolled women and men with HER2-negative ER-positive advanced breast cancer. Patients had disease relapse or progression during or after treatment with an aromatase inhibitor, with or without previous CDK4/6 inhibitor therapy. The trial included 708 patients: 289 patients (40.8%) had PIK3CA/AKT/PTEN pathway alterations and 489 (69.1%) received a prior CDK4/6 inhibitor for advanced breast cancer. Patients were randomly assigned in a 1:1 ratio to receive either capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed PFS which was measured both in the overall population and in patients with PIK3CA/AKT/PTEN pathway–altered tumors.[32]

The phase III, randomized, double-blind CAPITELLO-291 trial (NCT04305496) enrolled women and men with HER2-negative ER-positive advanced breast cancer. Patients had disease relapse or progression during or after treatment with an aromatase inhibitor, with or without previous CDK4/6 inhibitor therapy. The trial included 708 patients: 289 patients (40.8%) had PIK3CA/AKT/PTEN pathway alterations and 489 (69.1%) received a prior CDK4/6 inhibitor for advanced breast cancer. Patients were randomly assigned in a 1:1 ratio to receive either capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed PFS which was measured both in the overall population and in patients with PIK3CA/AKT/PTEN pathway–altered tumors.[32]

In the overall population, the median PFS was 7.2 months in the capivasertib-fulvestrant group versus 3.6 months in the placebo-fulvestrant group (HR, 0.60; 95% CI, 0.51–0.71; P < .001).[32][Level of evidence B1]

The phase III, randomized, double-blind CAPITELLO-291 trial (NCT04305496) enrolled women and men with HER2-negative ER-positive advanced breast cancer. Patients had disease relapse or progression during or after treatment with an aromatase inhibitor, with or without previous CDK4/6 inhibitor therapy. The trial included 708 patients: 289 patients (40.8%) had PIK3CA/AKT/PTEN pathway alterations and 489 (69.1%) received a prior CDK4/6 inhibitor for advanced breast cancer. Patients were randomly assigned in a 1:1 ratio to receive either capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed PFS which was measured both in the overall population and in patients with PIK3CA/AKT/PTEN pathway–altered tumors.[32]

In the PIK3CA/AKT/PTEN pathway-altered population, the median PFS was 7.3 months in the capivasertib-fulvestrant group and 3.1 months in the placebo-fulvestrant group (HR, 0.50; 95% CI, 0.38–0.65; P < .001).

The phase III, randomized, double-blind CAPITELLO-291 trial (NCT04305496) enrolled women and men with HER2-negative ER-positive advanced breast cancer. Patients had disease relapse or progression during or after treatment with an aromatase inhibitor, with or without previous CDK4/6 inhibitor therapy. The trial included 708 patients: 289 patients (40.8%) had PIK3CA/AKT/PTEN pathway alterations and 489 (69.1%) received a prior CDK4/6 inhibitor for advanced breast cancer. Patients were randomly assigned in a 1:1 ratio to receive either capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed PFS which was measured both in the overall population and in patients with PIK3CA/AKT/PTEN pathway–altered tumors.[32]

In patients who received capivasertib and fulvestrant, the most frequent grade 3 or higher adverse events were rash (12.1%) and diarrhea (9.3%). Grade 3 or higher rash and diarrhea occurred in 0.3% of patients who received placebo and fulvestrant. Adverse events sometimes led to treatment discontinuation. This occurred in 13.0% of the capivasertib-fulvestrant group and 2.3% of the placebo-fulvestrant group.