The combination of capivasertib plus fulvestrant significantly improved progression-free survival vs fulvestrant alone in patients with hormone receptor–positive/HER2-negative advanced breast cancer, including those with AKT pathway–altered tumors.
The combination of capivasertib plus fulvestrant (Faslodex) significantly improved progression-free survival (PFS) vs fulvestrant alone in patients with hormone receptor–positive/HER2-negative advanced breast cancer, including those with AKT pathway–altered tumors, according to data from the phase 3 CAPItello-291 trial (NCT04305496) presented during the 2022 San Antonio Breast Cancer Symposium.
The median PFS was 7.2 months in those receiving capivasertib plus fulvestrant vs 3.6 months in the placebo arm (HR, 0.60; 95% CI, 0.51-0.71; 2-sided P < .001). Patients had an objective response rate (ORR) of 22.9% in the capivasertib arm vs 12.2% in the placebo arm. In patients who had AKT pathway mutations, the median PFS was 7.3 months in the capivasertib arm and 3.1 months in the placebo arm (HR, 0.50; 95% CI, 0.38-0.65; 2-sided P < .001). Additionally, the ORR was 28.8% vs 9.7% in the capivasertib and placebo arms, respectively.
“The improvement in progression-free survival with relatively well-tolerated [adverse] effects is extremely encouraging,” Nicholas Turner, MD, PhD, lead author of the study said. “We are hopeful that capivasertib will become a new treatment option for patients whose cancer has progressed on a regimen containing an endocrine therapy.”
A total of 708 patients were randomly assigned 1:1 in the overall population to either the capivasertib plus fulvestrant (n = 355) arm or the placebo plus fulvestrant arm (n = 353). Those who had AKT pathway-altered tumors were also randomly assigned to either the capivasertib arm (n = 155) or the placebo arm (n = 134). Patients received 400 mg twice daily of capivasertib for 4 days on and 3 days off; 500 mg of fulvestrant during cycle 1 days 1 and 15 then every 4 weeks; with the placebo arm being matched.
The primary end points were PFS by investigator assessment both in the overall population and those with AKT pathway tumors, while the secondary end points included overall survival (OS) and ORR.
In the overall population, a majority of patients received 1 prior line of endocrine therapy (80.6% vs 71.4%) compared with the AKT altered-pathway tumors (83.9% vs 71.6%), additionally, previous CDK4/6 inhibitors were given between both the overall (69.0% vs 69.1%) and the AKT altered pathways (72.9% vs 67.9%), as well as previous adjuvant/neoadjuvant therapy in the overall population (50.7% vs 48.2%) and the AKT altered pathway (51.0% vs 50.0%) in the capivasertib vs placebo arms, respectively.
In the non-altered population, the investigator-assessed PFS was 7.2 months in the capivasertib arm vs 3.7 months in the placebo arm (HR, 0.70; 95% CI, 0.56-0.88). When PFS was assessed via the prespecified subgroup analysis, there was a consistent benefit seen in all groups.
The planned OS analysis, which was requested, showed a benefit between both groups in the overall population (HR, 0.74; 95% CI, 0.56-0.98) and the AKT altered-pathway group (HR, 0.69; 95% CI, 0.45-1.05).
Adverse effects of grade 3 or higher that were most common in those receiving capivasertib vs placebo included diarrhea (9.3% vs 0.3%), rash that was maculopapular (6.2% vs 0%), rash (5.4% vs 0.6%), hyperglycemia (2.3% vs 0.3%), and stomatitis (2.0% vs 0%). Discontinuation because of AEs occurred in 2.3% of patients in both the capivasertib and placebo arms.
Turner N, Oliveria M, Howell SJ, et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: results from the Phase III CAPItello-291 trial. Presented at the 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS3-04.