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William J. Gradishar, MD, FACP, FASCO


AKT Inhibitor Plus Hormone Therapy Approved by the FDA for Breast Cancer

By: JNCCN 360 Staff
Posted: Tuesday, November 21, 2023

On November 16, 2023, the U.S. Food and Drug Administration (FDA) approved the AKT inhibitor capivasertib (Truqap) with the hormone therapy fulvestrant in the treatment of adults with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer. These patients must have one or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, following disease 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 the FoundationOne CDx assay as a companion diagnostic to identify those with breast cancer for this combination therapy.

Efficacy of this combination therapy was evaluated in CAPItello-291 ( identifier NCT04305496), a randomized, double-blind, placebo-controlled, multicenter trial of 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer; 289 patients had tumors with PIK3CA/AKT1/PTEN alterations. All patients were required to have disease progression on aromatase inhibitor–based treatment.

A statistically significant difference in progression-free survival was observed in the overall population and in the population of patients whose tumors had PIK3CA/AKT1/PTEN alteration(s). In the 289 patients with PIK3CA/AKT1/PTEN-altered tumors, the median progression-free survival was 7.3 months with capivasertib plus fulvestrant and 3.1 months with a placebo plus fulvestrant (hazard ratio = 0.50 [95% confidence interval = 0.38–0.65] P < .0001).

The most common adverse reactions (reported in ≥ 20% of patients), including laboratory abnormities were 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 recommended capivasertib dose is 400 mg orally twice daily (approximately 12 hours apart), with or without food, for 4 days followed by 3 off days until disease progression or unacceptable toxicity. In the CAPItello-291 trial, fulvestrant was given at 500 mg intramuscularly on cycle 1 days 1 and 15 and then every 28 days thereafter.

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