On November 16, 2023, the U.S. Food and Drug Administration (FDA) approved capivasertib (Truqap™) with fulvestrant for adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1, or 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. FDA also approved the FoundationOne®CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with capivasertib with fulvestrant.

FDA update

Efficacy was evaluated in CAPItello-291 (NCT04305496), a randomized, double-blind, placebo-controlled, multicenter trial that involved 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, of which 289 patients had tumors with PIK3CA, AKT1, or PTEN alterations. All patients were required to have progression on aromatase inhibitor-based treatment. Patients could have received up to two prior lines of endocrine therapy and up to one line of chemotherapy for locally advanced or metastatic disease.

Patients were randomized 1:1 to receive either capivasertib 400 mg or placebo administered orally twice daily for four days, followed by three days off treatment, each week over a 28-day treatment cycle. Patients in both arms received fulvestrant 500 mg intramuscularly on cycle 1, days 1 and 15, and then every 28 days thereafter. Patients continued the therapy until they experienced disease progression or unacceptable toxicity.

The major efficacy outcome measure was investigator-assessed progression-free survival (PFS) in the overall population and in the population of patients whose tumors had PIK3CA, AKT1, or PTEN alterations evaluated according to RECIST version 1.1. A statistically significant difference in PFS was observed in the overall population and in the population of patients whose tumors had PIK3CA, AKT1, or PTEN alterations.

In the 289 patients with PIK3CA-, AKT1-, or PTEN-altered tumors, the median PFS was 7.3 months (95% CI = 5.5, 9.0) in the capivasertib-fulvestrant group and 3.1 months (95% CI = 2.0, 3.7) in the placebo-fulvestrant group (HR = 0.50; 95% CI = 0.38, 0.65; p < 0.0001).

An exploratory analysis of PFS in the 313 patients whose tumors did not have a PIK3CA, AKT1, or PTEN alteration showed a HR of 0.79 (95% CI = 0.61, 1.02), indicating that the difference in the overall population was primarily attributed to the results seen in the population of patients whose tumors have PIK3CA, AKT1, or PTEN alterations.

The most common adverse reactions, including laboratory abnormities, reported in at least 20% of patients receiving capivasertib 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 four days followed by three off days until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for capivasertib.

The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, Israel’s Ministry of Health, Singapore’s Health Sciences Authority, Switzerland's Swissmedic, and United Kingdom’s Medicines and Healthcare Products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The FDA approved this application two weeks ahead of its goal date. The application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications for oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.