Fulvestrant Plus Capivasertib Prolongs PFS in HR+ Locally Advanced Metastatic Breast Cancer

A progression-free survival advantage and trend toward overall survival benefit has been demonstrated in the CAPItello-291 study of capivasertib and fulvestrant for the treatment of hormone receptor-positive, HER2-low or negative locally advanced or metastatic breast cancer.

The combination of capivasertib (AZD5363) and fulvestrant (Faslodex) showed statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with placebo plus fulvestrant in patients with hormone receptor (HR)-positive, HER2-low or negative locally advanced or metastatic breast cancer, following recurrence or progression on or after endocrine therapy.1

According to an announcement about the phase 3 CAPItello-291 study (NCT04305496), capivasertib/fulvestrant achieved PFS improvement in the overall patient population and in a prespecified biomarker subgroup of patients with alterations in the PIK3CA, AKT1 or PTEN genes. Both primary end points of the study were met.

Moreover, a trend toward overall survival (OS) benefit was demonstrated with capivasertib/fulvestrant. The safety profile of the combination appeared similar to previous studies.

“The CAPItello-291 phase 3 trial results show capivasertib offers a clinically meaningful improvement in progression free survival for patients with HR-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,” said Nicholas Turner, MD, PhD, professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, in a press release.

CAPItello-291 is a double-blind, randomized trial. The ongoing study is actively enrolling 834 patients who will be assigned fulvestrant 500 mg administered on day 1 of weeks 1 and 3 of cycle 1, and then on day 1, week 1 of each cycle thereafter in combination with capivasertib 400 mg given in 2 oral tablets on an intermittent weekly dosing schedule in the experimental arm. Capivasertib will be administered on days 1 to 4 in each week of a 28-day treatment cycle.

In the comparator arm, patients will receive matching fulvestrant and placebo.2

As secondary end points, the study is exploring overall survival, time from randomization to second progression by investigator assessment, response rate in the overall population, duration of response, clinical benefit rate, the occurrence and frequency of adverse events, plasma concentration of capivasertib, quality of life, and time to definitive deterioration of the ECOG performance statues.

Patients are eligible to enroll in CAPItello-291 if they have histologically confirmed HR+/HER2- breast cancer that is metastatic or locally advanced. Patients are required to have an ECOG or WHO performance score of 0-1, measurable disease per RECIST, and be eligible for treatment with a regimen that contains an aromatase inhibitor. Patients can be treated at 266 study locations worldwide.

“These exciting data in an all-comers population indicate that capivasertib could become a new first-in-class treatment option for patients with HR-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, Oncology R&D, AstraZeneca, stated in the press release.


1. 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 26, 2022. https://bit.ly/3FjyAAD

2. Capivasertib+fulvestrant vs placebo+fulvestrant as treatment for locally advanced (inoperable) or metastatic HR+/HER2- breast cancer (CAPItello-291). ClinicalTrials.gov. Updated October 4, 2022. Accessed October 26, 2022. https://clinicaltrials.gov/ct2/show/NCT04305496?term=CAPItello-291&draw=2&rank=1