FDA approves capivasertib with fulvestrant for breast cancer

FDA approval (Nov 16, 2023)

The FDA approved capivasertib (Truqap; AstraZeneca) with fulvestrant for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.

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

Key efficacy evidence: CAPItello-291 (NCT04305496)

CAPItello-291 was a randomized, double-blind, placebo-controlled, multicenter trial (N=708) in locally advanced/metastatic HR-positive, HER2-negative breast cancer; 289 patients had PIK3CA/AKT1/PTEN-altered tumors. All patients had progression on aromatase inhibitor–based therapy.

Primary efficacy outcome was investigator-assessed PFS (RECIST v1.1) in the overall population and the altered-tumor subgroup; a statistically significant PFS difference was reported in both.

In the PIK3CA/AKT1/PTEN-altered subgroup, median PFS was 7.3 months with capivasertib–fulvestrant vs 3.1 months with placebo–fulvestrant (HR 0.50, 95% CI 0.38–0.65; p<0.0001). An exploratory PFS analysis in patients without these alterations showed HR 0.79 (95% CI 0.61–1.02).

Safety and dosing (per FDA summary)

Common adverse reactions (≥20%; including labs) included diarrhea, cutaneous adverse reactions, hyperglycemia (random/fasting glucose), cytopenias, nausea, fatigue, vomiting, and stomatitis. Recommended dose: capivasertib 400 mg orally twice daily, 4 days on/3 days off.

Review occurred under Project Orbis; reviews at other agencies were ongoing.