FDA Grants Priority Review to Capivasertib Combination for Locally Advanced, Metastatic Breast Cancer


Capivasertib combined with fulvestrant doubled progression-free survival in patients with recurrent or progressed advanced stage HR-positive HER2-negative breast cancer compared to placebo.

The FDA has granted priority review to a new drug application (NDA) for capivasertib combined with fulvestrant (Faslodex; AstraZeneca) for adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer (BC) following recurrence or progression on or after an endocrine-based regimen.

The FDA granted the NDA with priority review based on data from the phase 3 CAPItello-291 trial, which compared capivasertib combined with fulvestrant to fulvestrant combined with placebo. The capivasertib combination was shown to reduce the risk of disease progression or death by 40% compared to placebo.

“This priority review decision underscores the potential of capivasertib to extend the effectiveness of endocrine-based treatment approaches for patients with HR-positive BC who experience tumor progression on, or resistance to these widely used therapies,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in a press release.

During the phase 3 trial, capivasertib combined with fulvestrant was also shown to double progression-free survival compared to placebo at 7.2 vs 3.6 months, respectively. There are no mature overall safety (OS) data, but early data are encouraging. Further, the safety profile of capivasertib was similar to data found in previous trials.

More than 65% of BC tumors are HR-positive and HER2-low or negatives. Estrogen receptors drive the growth of BC cells in HR-positive tumors. First-line treatment includes endocrine therapies combined with cyclin-dependent kinase (CDK) 4/6 inhibitors, but resistance often occurs in advanced disease. Chemotherapy is the next line of treatment, but survival outcomes beyond 5 years decrease significantly to 30%.

Capivasertib is anAKT (Ak strain transforming) inhibitor that inhibits all 3 AKT isoforms. It is under investigation with other therapies to target tumor alterations in the AKT pathway. It is indicated as a 400 mg dose administered 2 times daily—in compliance with an intermittent dosing schedule of 4 days on and 3 days off—based on early trial evaluation.

CAPItello-291 is a phase 3, double-blind, randomized trial evaluating the efficacy of capivasertib combined with fulvestrant compared to fulvestrant combined with placebo for locally advanced or metastatic HR-positive, HER2-low or negative BC. The trial included 708 patients with recurrence while on, or after, aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to 1 line of chemotherapy for advanced disease.

Data from the phase 3 trial were originally presented at the 2022 San Antonio Breast Cancer Symposium (SABCS) and recently published online in The New England Journal of Medicine. In January 2023, the FDA granted capivasertib with Fast Track Designation.

Galbraith concluded that AstraZeneca “look(s) forward to working with the FDA to bring this potential first-in-class AKT inhibitor to patients as quickly as possible.”


AstraZeneca. Capivasertib in combination with Faslodex granted Priority Review in the US for patients with advanced HR-positive BC. News Release. June 12, 2023. Accessed on June 12, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/capivasertib-in-combination-with-faslodex-granted-priority-review-in-the-us.html

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