Capivasertib Receives FDA Approval for Advanced Breast Cancer Treatment

For adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer that progressed after at least one endocrine-based regimen in the metastatic setting or recurred within 12 months of completing adjuvant therapy, and with one or more PIK3CA/AKT1/PTEN alterations detected by an FDA-approved test, the approved drug is capivasertib (Truqap, AstraZeneca Pharmaceuticals). The Food and Drug Administration (FDA) in the United States approved its use with fulvestrant on 16 November 2023.

The FDA also approved FoundationOne®CDx as a companion diagnostic to identify breast cancer patients for capivasertib plus fulvestrant.

Capivasertib is a small-molecule drug that inhibits the AKT signaling pathway . Developed by AstraZeneca, it targets a pathway controlling cell growth and division. The pathway becomes overactive in some cancers, potentially causing uncontrolled cell growth and progression. By inhibiting it, capivasertib slows cancer-cell growth and may help prevent cancer progression.

FDA Approval Based on the CAPItello-291 Trial

CAPItello-291, a phase 3, randomized, double-blind trial, enrolled patients whose disease relapsed or progressed during or after aromatase inhibitor treatment, with or without prior cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Participants were premenopausal, perimenopausal, or postmenopausal women and men with HR-positive, HER2-negative advanced breast cancer.

Patients were randomly assigned 1:1 to capivasertib plus fulvestrant or placebo plus fulvestrant.

The study had dual primary endpoints: investigator-assessed outcomes in the overall population and in tumors with AKT-pathway alterations (PIK3CA, AKT1, or PTEN), measured as progression-free survival.

Results

The study enrolled 708 patients; 289 (40.8%) had AKT-pathway alterations, and 489 (69.1%) had previously received a CDK4/6 inhibitor for advanced breast cancer.

• In the overall population, median progression-free survival was 7.2 months with capivasertib–fulvestrant and 3.6 months with placebo–fulvestrant (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001).
• Among patients with AKT-pathway alterations, median progression-free survival was 7.3 months with capivasertib–fulvestrant and 3.1 months with placebo–fulvestrant (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001).

The most common grade 3 or higher side effects with capivasertib–fulvestrant were rash (12.1% versus 0.3%) and diarrhea (9.3% versus 0.3%). Treatment discontinuation due to side effects occurred in 13% of the capivasertib arm and 2.3% of the placebo arm.

The recommended capivasertib dose is 400 mg twice daily, approximately 12 hours apart, with or without food, for 4 days followed by a 3-day break, until disease progression or unacceptable toxicity.

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