FDA Approves Capivasertib With Fulvestrant for PIK3CA/AKT1/PTEN Alterations Breast Cancer


Capivasertib is indicated for hormone receptor-positive, human epidermal growth factor 2-negative locally advanced or metastatic breast cancer with 1 or more PIK3CA/ALT1/PTEN-alterations.

The FDA has approved capivasertib (Truqap; AstraZeneca Pharmaceuticals) in combination with fulvestrant (Faslodex; AstraZeneca Pharmaceuticals) for the treatment of hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative locally advanced or metastatic breast cancer with 1 or more PIK3CA/AKT1/PTEN alterations, as detected by an FDA-approved test, according to a press release from the agency.1

The regimen should follow progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing an adjuvant therapy, according to the indication. The recommended dose is 400 mg orally, twice daily at approximately 12 hours apart, with or without food. This continues for 4 days, followed by 3 days off treatment, until disease progression or unacceptable toxicity.1

In addition, the FDA also approved the FoundationOneCDx assay, a companion diagnostic device, to identify individuals with breast cancer for treatment with the regimen.1

According to a study published in Breast Cancer Research and Treatment, the PIK3CA/AKT1/PTEN alterations account for approximately 50% of HR+ breast cancers, creating resistance to endocrine therapies.2

The approval was based on results from a randomized, placebo-controlled, multicenter trial including 708 individuals who had locally advance or metastatic HR+, HER2- breast cancer, including 289 individuals who had PIK3CA/AKT1/PTEN alterations in the tumors. The CAPItello-291 (NCT04305496) trial also required individuals to have progression on an aromatase inhibitor-based treatment, which could include 2 prior lines of endocrine therapy and up to 1 line of chemotherapy.1

About The CAPItello-291 Trial

Trial Name: Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/​HER2- Breast Cancer

ClinicalTrials.gov ID: NCT04305496

Sponsor: AstraZeneca

Completion Date: August 2022

The investigators of the study assigned individuals to receive either 400 mg of capivasertib or the placebo, orally administered twice daily. This was followed by 3 days off treatment each week, over a 28-day cycle, according to the press release. Both arms received fulvestrant 500 mg as an intramuscular injection on cycle 1, days 1 and 15, followed by every 28 days after the first cycle. Treatment continued until either disease progression or unacceptable toxicity.1

Progression-free survival (PSF) in the overall population, and in those with PIK3CA/AKT1/PTEN alterations in the tumors, was the major efficacy outcome of the study. It was evaluated in accordance with RECIST, version 1.1, according to the press release. The investigators found that there was a statistically significant difference in PFS for the overall population and those with PIK3CA/AKT1/PTEN alterations in the tumors.1

For the individuals with PIK3CA/AKT1/PTEN-alterations in the tumors, the median PFS was 7.3 months in the capivasertib group compared to 3.1 months in the placebo group. Furthermore, approximately 44% of those without the PIK3CA/AKT1/PTEN alterations demonstrated a hazard ratio of 0.79 compared to 0.50 for those who had the alteration, which investigators said showed the difference in the overall population was attributed what was seen in the PIK3CA/AKT1/PTEN alterations patient population.1

Pharmacy Times Oncology Edition Call For Papers

Pharmacy Times Oncology Edition Call For Papers

Common adverse reactions 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, according to the press release.1

The application was granted priority reviews by the FDA and was approved 2 weeks ahead of the FDA goal date since it was reviewed using the Assessment Aid submission.1


  1. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 17, 2023. Accessed November 17, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer
  2. Turner N, Dent RA, O'Shaughnessy J, Kim SB, et al. Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial. Breast Cancer Res Treat. 2022;191(3):565-576. doi:10.1007/s10549-021-06450-x
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