US - FDA Approves AZ’s Truqap (capivasertib) Plus Faslodex (fulvestrant) for Advanced HR+ HER2- Breast Cancer

On Nov. 17, 2023, US FDA approved AZ’s Truqap (capivasertib) in combination with Faslodex (fulvestrant, an endocrine therapy) for HR+ HER2- locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) as detected by an FDA-approved test. Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced 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.

Of note to Regulatory Affairs:

·       This review used Project Orbis. FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Israel’s Ministry of Health (IMoH), Singapore’s Health Sciences Authority (HSA), Switzerland’s Swissmedic, and United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.

·       This application was granted Priority Review. Assessment Aid, a voluntary submission from the applicant, was used to facilitate FDA review.

CAPItello-291 (NCT04305496) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 trial. Patients were randomized (1:1) to either capivasertib + fulvestrant or placebo + fulvestrant treatment.

Among 708 patients with locally advanced or metastatic HR-positive HER2-negative breast cancer, 289 patients had tumors with PIK3CA/AKT1/PTEN-alterations.

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/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 have PIK3CA/AKT1/PTEN-alteration(s).

In the 289 patients with PIK3CA/AKT1/PTEN-altered tumors, the median PFS was 7.3 months (95% CI: 5.5, 9.0) in the capivasertib+fulvestrant group vs. 3.1 months (95% CI: 2.0, 3.7) in the placebo+fulvestrant group (Hazard Ratio [HR] 0.50 [95% CI: 0.38, 0.65]).

An exploratory analysis of PFS in the 313 (44%) patients whose tumors did not have a PIK3CA/AKT1/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/PTEN-alteration.

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.

Link to FDA announcement

Link to AZ press release