Capivasertib Plus Fulvestrant Approved for Patients With HR-Positive, HER2-Negative Breast Cancer

On November 16, 2023, the US Food and Drug Administration (FDA) approved capivasertib plus fulvestrant for patients with previously treated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer harboring one or more PIK3CA/AKT1/PTEN-alteration, as detected by an FDA-approved test. 

This approval was based on efficacy findings from the phase 2 double-blind, placebo-controlled, multicenter, CAPItello-291 study. In this study, 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, previously treated with up to 2 lines of endocrine therapy and up to 1 line of chemotherapy for locally advanced or metastatic disease were enrolled. Enrollment required patients to have experienced disease progression after treatment with an aromatase inhibitor-based agent.

Patients were randomized on a 1-to-1 basis to receive either 400 mg capivasertib twice daily or placebo for 4 days, followed by 3 days off over a 28-day treatment cycle, followed by 500 mg of intramuscular fulvestrant on cycle 1 days 1 and 15, followed by administration every 28 days thereafter until disease progression or unacceptable toxicity. The major efficacy outcome measure was investigator assessed progression-free survival (PFS) in both patients with (n = 289) and without (n = 313) PIK3CA/AKT1/PTEN-alterations, evaluated according to RECIST v 1.1 guidelines. 

At the time of analysis, there was a statistically significant difference in PFS observed between patients with and without PIK3CA/AKT1/PTEN-alterations. Among patients with PIK3CA/AKT1/PTEN-alterations, the median PFS was 7.3 months in the capivasertib-fulvestrant arm and 3.1 months in the placebo arm (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.38 to 0.65; P = < 0.0001). Results from an exploratory analysis of patients without PIK3CA/AKT1/PTEN-alterations showed a HR of 0.79, demonstrating that outcome differences could be attributed to results from patients with PIK3CA/AKT1/PTEN-alterations.

The most common adverse events reported in ≥20% of patients included diarrhea, cutaneous adverse reactions, increased random glucose, decreased lymphocytes, decreased hemoglobin, increased fasting glucose, nausea, fatigue, decreased leukocytes, increased triglycerides, decreased neutrophils, increased creatinine, vomiting, and stomatitis. 

The FDA has additionally approved FoundationOne CDx assay as a companion diagnostic device to identify patients eligible for treatment with capivasertib plus fulvestrant. 

The recommended dose of capivasertib is 400 mg orally, twice daily, taken approximately 12 hours apart, with or without food for 4 days followed by 3 days off treatment until disease progression or unacceptable toxicity.

Source: 

FDA approves capivasertib with fulvestrant for breast cancer. US Food and Drug Administration. Published November 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer