FDA Approves Companion Diagnostic for Capivasertib Plus Fulvestrant in Advanced HR+/HER2–Breast Cancer


The FDA has approved the FoundationOne® CDx for use as a companion diagnostic to identify patients with advanced hormone receptor–positive, HER2-negative advanced breast cancer who may be eligible for treatment with the combination of capivasertib and fulvestrant.



The FDA has approved the FoundationOne® CDx for use as a companion diagnostic to identify patients with advanced hormone receptor–positive, HER2-negative advanced breast cancer who may be eligible for treatment with the combination of capivasertib (Truqap) and fulvestrant (Faslodex).1

On November 16, 2023, the FDA approved capivasertib plus fulvestrant for the treatment of adult patients with locally advanced or metastatic, hormone receptor–positive, HER2-negative breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations, as detected by an FDA-approved test, following progression on at least 1 endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.2

FoundationOne CDx is a next-generation sequencing–based in vitro diagnostic device designed to detect substitutions, insertion, and deletion alterations, as well as copy number alterations in 324 genes and select gene rearrangements through a tissue sample. Additionally, the test can identify genomic signatures such as microsatellite instability and tumor mutational burden.1

“We are thrilled to see an additional therapeutic option approved to help treat the high number of [patients with] hormone receptor–positive breast cancer,” Troy Schurr, chief biopharma business officer at Foundation Medicine, stated in a news release.1 “This companion diagnostic approval adds to the growing utility of Foundation Medicine’s high-quality diagnostic test portfolio in treating advanced breast cancer.”

The approval of the capivasertib plus fulvestrant was supported by data from the phase 3 CAPItello-291 trial (NCT04305496), where findings showed that the combination reduced the risk of progression or death by 50% vs placebo plus fulvestrant in patients with PIK3CA/AKT1/PTEN-altered tumors (HR, 0.50; 95% CI, 0.38, 0.65; P < .0001). Patients in this population treated in the capivasertib arm (n = 155) achieved a median progression-free survival (PFS) of 7.3 months (95% CI, 5.5-9.0) vs 3.1 months (95% CI, 2.0-3.7) for placebo plus fulvestrant (n = 134).3

In the overall population, irrespective of PIK3CA/AKT1/PTEN mutational status, patients treated in the capivasertib arm (n = 355) experienced a median PFS of 7.2 months (95% CI, 5.5-7.4) vs 3.6 months (95% CI, 2.8-3.7) for those given placebo plus fulvestrant (n = 353; HR, 0.60; 95% CI, 0.51-0.71; P < .001).

CAPItello-291 was a randomized, double-blind, placebo-controlled, multicenter trial that included 708 patients with locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer, including 289 patients whose tumors harbored PIK3CA/AKT1/PTEN alterations.2 Patients needed to be at least 18 years of age with histologically confirmed disease following recurrence or progression during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to 1 line of chemotherapy for advanced disease.3

Investigators randomly assigned patients in a 1:1 fashion to receive 400 mg of oral capivasertib or placebo twice per day for 4 days, followed by 3 days off, in 28-day treatment cycles. In both arms, patients were administered 500 mg of intramuscular fulvestrant on days 1 and 15 of cycle 1, then once every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity occured.

PFS in the overall patient population and in the population of patients whose tumors harbored PIK3CAAKT1 or PTEN alterations in the AKT pathway served as the trial’s co-primary end points. Secondary end points included overall survival, objective response rate, and safety.

The most common adverse effects that occurred in at least 20% of patients treated in the capivasertib arm 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.2

“The prevalence of hormone receptor–positive breast cancer means the introduction of new targeted treatment options for this patient population will have an exponential impact,” Shehzin Tietjen, associate director of corporate relations at Living Beyond Breast Cancer, said in a news release.1 “Biomarker testing is such an important component of getting patients on the right therapy for their specific cancer, and we’re encouraged to see additional companion diagnostic indications being approved to help increase patient access to precision medicine.”


  1. U.S. FDA approves FoundationOne CDx as a companion diagnostic for AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) to identify patients with HR-positive, HER2-negative advanced breast cancer. News release. Foundation Medicine. November 20, 2023. Accessed November 21, 2023. https://www.foundationmedicine.com/press-release/us-fda-approves-foundationonercdx-companion-diagnostic-astrazenecas-truqaptm-0
  2. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed November 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer
  3. Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor–positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070. doi:10.1056/NEJMoa2214131
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