PFS Benefit Observed Following Capivasertib/Fulvestrant in HR+ HER2-Low Locally Advanced Breast Cancer


The addition of capivasertib to fulvestrant resulted in a statistically significant and clinically meaningful improvement in progression-free survival for patients with hormone receptor–positive, HER2-low-or -negative locally advanced or metastatic breast cancer.

A statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed when patients with hormone receptor–positive, HER2-low-or-negative locally advanced or metastatic breast cancer received treatment with capivasertib and fulvestrant vs placebo plus fulvestrant following progression on or after endocrine therapy plus or minus a CDK4/6 inhibitor, according to a press release from AstraZeneca regarding the phase 3 CAPItello-291 trial (NCT04305496).

In addition to meeting the primary end point of PFS in the overall patient population, the trial also met the primary end point of improved PFS across several prespecified biomarker subgroups, including PIK3CA, AKT1, or PTEN gene alterations. Overall survival (OS) data, the study’s key secondary end point, were encouraging despite being early; further assessment of OS will take place. Data from the study are set to be presented at an upcoming medical meeting.

“The CAPItello-291 phase 3 trial results show capivasertib offers a clinically meaningful improvement in progression-free survival for patients with hormone receptor–positive breast cancer. This potential new medicine could give people more time with their cancer under control, which is a priority for patients and their families,” principal investigator Nicholas Turner, MD, PhD, professor of Molecular Oncology at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK, said in the press release.

The trial included a total of 708 patients with histologically confirmed disease. Patients were treated with 400 mg of oral capivasertib given on an intermittent weekly schedule on days 1 to 4 or matched placebo plus 500 mg of an intramuscular injection of fulvestrant on day 1 of weeks 1 and 3 in cycle 1 and day 1 of week 1 of each subsequent cycle.

Additional secondary outcomes included time to second objective disease progression (PFS2), overall response rate, duration of response, clinical benefit rate, and safety.

The trial included patients who were pre- and post-menopausal, as well as male patients. Patients were required to have an ECOG/World Health Organization performance status of 0 or 1, have previously been treated with an aromatase inhibitor containing regimen, and have measurable disease.

The safety profile in the combination arm was similar to that of what was previously reported in other trials which evaluated capivasertib plus fulvestrant.

“These exciting data in an all-comers population indicate that capivasertib could become a new first-in-class treatment option for patients with hormone receptor–positive breast cancer. These patients often experience tumor progression on, or resistance to, available endocrine therapies for advanced disease and urgently need new therapies that extend the effectiveness of endocrine-based treatment approaches,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, concluded.


Capivasertib plus Faslodex significantly improved progression-free survival vs. Faslodex in CAPItello-291 phase III trial in advanced HR-positive breast cancer. News release. AstraZeneca. October 26, 2022. Accessed October 28, 2022.

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