Results from the phase 3 CCTG/BCT MA.40/FINER study demonstrated that ipatasertib plus fulvestrant significantly prolonged progression-free survival (PFS) among patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. 

These data were first presented by Stephen Chia, MD, The University of British Columbia, Vancouver, British Columbia, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this double-blind trial, researchers randomized 250 pre, peri, and postmenopausal patients who experienced disease progression after first-line treatment with a CDK4/6 inhibitor plus and an aromatase inhibitor on a 1-to-1 basis to receive either ipatasertib or placebo plus fulvestrant. Patients were stratified based on AKT pathway alterations (n = 111), wild-type status, and endocrine resistance. The primary end point was PFS in the intention-to-treat population. Key secondary end points included PFS in AKT-altered patients and safety. 

At a median follow-up of 15.2 months, median PFS in the intention-to-treat population was 5.32 months in the ipatasertib arm and 1.94 months in the placebo arm (hazard ratio [HR] 0.61; 95% confidence interval [CI], 0.46 to 0.81; P = .0007). Median PFS in the AKT-altered population was 5.45 months in the ipatasertib arm and 1.91 months in the placebo arm (HR 0.47; 95% CI, 0.31 to 0.72; P = .0005). Grade ≥ 3 adverse events occurred in 37.1% of patients in the ipatasertib arm and 27.4% of patients in the placebo arm. The most frequent grade ≥ 3 non-hematological treatment-related adverse events occurring in > 1% of patients included diarrhea, fatigue, vomiting, and rash. Treatment discontinuation due to adverse events occurred in 6.5% of patients in the ipatasertib arm and .8% of patients in the placebo arm. 

“Ipatasertib plus fulvestrant significantly prolongs PFS compared to placebo/fulvestrant in patients with hormone receptor–positive [metastatic breast cancer] post progression on 1st line CDK 4/6 inhibitor and AI,” concluded Dr Chia et al. “Follow-up and additional analyses continue.”

Source: 

Chia SA, Redfern AD, Avoub JPM, et al. A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for advanced HER-2 negative and estrogen receptor positive (ER+) breast cancer following progression on first line CDK 4/6 inhibitor and aromatase inhibitor: The CCTG/BCT MA.40/FINER study (NCT04650581). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA1005