Results from the phase 3 CAPItello-291 clinical trial show that the combination doubled the median progression-free survival compared with the placebo in patients with HR-positive, HER2-negative advanced breast cancer.
Adding the investigational AKT inhibitor capivasertib to fulvestrant (Faslodex) significantly improved progression-free survival (PFS) in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC), according to results from the phase 3 CAPItello-291 trial (NCT4305496) presented at a press conference at the San Antonio Breast Cancer Symposium in Texas on December 8, 2022.1
The study results showed a 40% lower risk of progression among patients on capivasertib plus fulvestrant. Individuals treated with capivasertib plus fulvestrant had a clinically meaningful and statistically significant median PFS of 7.2 months compared with 3.6 months in those treated with a placebo plus fulvestrant. The objective response rate (ORR) was 22.9% among patients treated with capivasertib plus fulvestrant compared with 12.2% for those treated with a placebo plus fulvestrant.1,2
In the study, 41% of patients assigned to treatment had tumors with AKT pathway mutations. Among these patients treated with capivasertib plus fulvestrant, the median PFS was 7.3 months, and the ORR was 28.8%. Among patients with AKT pathway mutations treated with a placebo plus fulvestrant, the median PFS was 3.1 months, and the ORR was 9.7%.1
Many HR-positive/HER2-negative breast cancers have genetic mutations in AKT pathway genes, such as AKT, PIK3CA, and PTEN, which promote tumor growth and may lead to endocrine resistance.1
Investigators conducted the CAPItello-291 trial to determine whether the addition of the potential first-in-class AKT inhibitor capivasertib to fulvestrant would improve outcomes in patients with HR+ breast cancer whose tumors had developed resistance to an aromatase inhibitor. They randomly assigned 355 patients to receive capivasertib plus fulvestrant and 353 patients to receive a placebo plus fulvestrant.1
First-line therapy for patients with HR-positive/HER2-negative breast cancer is typically endocrine therapy (ET), such as an aromatase inhibitor, in conjunction with a CDK4/6 inhibitor.1
“After progression on CDK4/6 inhibitors, further [ETs] given alone have relatively low efficacy,” Nicholas Turner, MD, PhD, a professor of molecular oncology at The Institute of Cancer Research and a consultant medical oncologist at the Royal Marsden NHS Foundation Trust, both in London, who discussed the study in a SABCS press conference and later at a presentation at the symposium, said in a statement. “We need new treatment options for these patients.”1
In the study, the most common adverse events (AEs) of grade 3 or higher among patients treated with capivasertib plus fulvestrant were rashes, diarrhea, and hyperglycemia. The rate of discontinuation because of AEs was 13% among patients who received capivasertib plus fulvestrant and 2.3% among patients who received a placebo plus fulvestrant.1
The AE profile was consistent with data from previous studies, Turner said.1
“The improvement in [PFS] with relatively well-tolerated [AEs] is extremely encouraging,” he said. “We are hopeful that capivasertib will become a new treatment option for patients whose cancer has progressed on a regimen containing an [ET].”1
The study’s primary endpoints were PFS both overall and for those with AKT pathway tumors, while secondary endpoints included ORR and overall survival (OS).2
A limitation of this study was immature OS data, according to the statement.1
1. Adding capivasertib to fulvestrant improves progression-free survival in patients with advanced hormone receptor-positive breast cancer. News release. December 8, 2022. Accessed December 8, 2022. https://www.aacr.org/about-the-aacr/newsroom/news-releases/adding-capivasertib-to-fulvestrant-improves-progression-free-survival-in-patients-with-advanced-hormone-receptor-positive-breast-cancer/
2. Turner N. 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: San Antonio Breast Cancer Symposium; Henry B. Gonzalez Convention Center in Texas: December 8, 2022.