Capivasertib Plus Fulvestrant Yields PFS Improvement in HR+ Locally Advanced or Metastatic Breast Cancer


Capivasertib plus fulvestrant generated a statistically and clinically significant improvement in progression-free survival in select patients with hormone receptor–positive, HER2-low or -negative, locally advanced or metastatic breast cancer.

Nicholas Turner, MD, PhD

Nicholas Turner, MD, PhD

Capivasertib plus fulvestrant (Faslodex) generated a statistically and clinically significant improvement in progression-free survival (PFS) 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, with or without a CDK4/6 inhibitor, according to data from the phase 3 CAPItello-291 trial (NCT04305496).1

Preliminary results show the combination met both primary end points for PFS compared with fulvestrant alone in the overall population and in a prespecified biomarker subgroup of patients whose tumors had PIK3CA, AKT1, or PTEN alterations. Notably, patients with PIK3CA, AKT1, or PTEN alterations comprised approximately 40% of the overall population. Data for the key secondary end point of overall survival were immature, though early data are encouraging.

Investigators plan to present detailed findings at an upcoming medical conference.

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

The double-blind, randomized CAPItello-291 trial is evaluating the efficacy and safety of the investigational AKT inhibitor capivasertib in combination with fulvestrant in patients with histologically confirmed HR-positive, HER2-low or -negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to 1 line of chemotherapy for advanced disease. Patients are also required to have measurable disease per RECIST v1.1 criteria and an ECOG or WHO performance status of 0 or 1.2

Key exclusion criteria include symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy; more than 2 lines of endocrine therapy or more than 1 line of chemotherapy for inoperable locally advanced or metastatic disease; or prior treatment with AKT, PI3K and mTOR inhibitors, fulvestrant, or any other selective estrogen receptor degraders. No other chemotherapy, immunotherapy, immunosuppressant medication, or anticancer agents were permitted within 3 weeks prior to study treatment initiation.

The trial has enrolled 708 patients who were randomly assigned to 400 mg of oral capivasertib or placebo twice daily on days 1 to 4 of each week in a 28-day treatment cycle plus 2 intramuscular injections of fulvestrant at 500 mg given on day 1 of weeks 1 and 3 of cycle 1. The treatment is then administered on day 1 of week 1 of each cycle thereafter.

Other secondary end points include time to second progression, overall response rate, duration of response, and clinical benefit rate in the overall and PIK3CA, AKT1, or PTEN–altered populations, plus safety.

“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,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said. “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.”


  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.
  2. Capivasertib+fulvestrant vs placebo+fulvestrant as treatment for locally advanced (inoperable) or metastatic HR+/HER2- breast cancer (CAPItello-291). Updated October 4, 2022. Accessed October 26, 2022.
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