FDA Oks FoundationOne®CDx for Capivasertib/Fulvestrant in Breast Cancer

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In addition to the approval of capivasertib and fulvestrant, the FDA has granted approval to the FoundationOne® CDx as a companion diagnostic to identify patients with advanced HR-positive, HER2-negative advanced breast cancer.

  • FoundationOne CDx is a next-generation sequencing-based in vitro diagnostic device.

  • Capivasertib (Truqap) with fulvestrant (Faslodex) was granted approval by the FDA on November 16, 2023, for adult patients with locally advanced or metastatic, hormone receptor (HR)-positive, HER2-negative breast cancer harboring 1 or more PIK3CA, AKT1, or PTEN alterations.

  • This companion diagnostic approval adds a new high-quality diagnostic test to aid in the treatment of advanced breast cancer.

The FDA has granted approval to the FoundationOne® CDx as a companion diagnostic to identify patients with advanced HR-positive, HER2-negative advanced breast cancer who may be eligible for treatment with the combination of capivasertib and fulvestrant.1

FoundationOne CDx is a next-generation sequencing-based in vitro diagnostic device that works to detect substitutions, insertion, and deletion alterations. The device also can copy number alterations in 324 genes, select gene rearrangements through a tissue sample, and is able to identify genomic signatures, including microsatellite instability and tumor mutational burden.1

The combination of capivasertib with fulvestrant was granted approval by the FDA on November 16, 2023, for adult patients with locally advanced or metastatic, HR-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, based on findings from the phase 3 CAPItello-291 trial (NCT04305496).2

3d rendered medically accurate illustration of a females mammary glands cancer: © SciePro - stock.adobe.com

3d rendered medically accurate illustration of a females mammary glands cancer: © SciePro - stock.adobe.com


“We are thrilled to see an additional therapeutic option approved to help treat the high number of [patients with] hormone receptor–positive breast cancer,” said Troy Schurr, chief biopharma business officer at Foundation Medicine, 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 randomized, double-blind, placebo-controlled, multicenter CAPItello-291 study included 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer. A total of 289 patients had tumors that harbored PIK3CA/AKT1/PTEN alterations.2

Patients 18 years of age or older with histologically confirmed disease after 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 were randomized to receive 400 mg of oral capivasertib or placebo twice daily for 4 days, followed by 3 days off, in 28-day treatment cycles. Patients in both arms were given 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 occurred.

The primary end points of the study were progression-free survival (PFS) in the overall patient population and in the population of patients whose tumors harbored PIK3CA, AKT1 or PTEN alterations. Secondary end points consisted of overall survival, objective response rate, and safety.

In the CAPItello-291 trial, the combination of capivasertib and fulvestrant led to a reduced risk of progression or death by 50% vs the combination of placebo plus fulvestrant among patients with PIK3CA/AKT1/PTEN-altered tumors (HR, 0.50; 95% CI, 0.38-0.65; P <.0001). Among the 155 patients given treatment with the capivasertib/fulvestrant combination, the median PFS was 7.3 months (95% CI, 5.5-9.0) vs 3.1 months (95% CI, 2.0-3.7) in the 134 patients given placebo plus fulvestrant.3

In the overall population, patients treated in the capivasertib arm (n = 355) had 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). This was irrespective of PIK3CA/AKT1/PTEN mutational status.

For safety, the most frequently reported adverse effects occurring in at least 20% of patients given capivasertib plus fulvestrant 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.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,” said Shehzin Tietjen, associate director of corporate relations at Living Beyond Breast Cancer, in a press 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.”

REFERENCES
  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://tinyurl.com/2p92bwfr
  2. FDA approves capivasertib with fulvestrant for breast cancer. News release. FDA. November 16, 2023. Accessed November 21, 2023. https://tinyurl.com/2m5rh4jz
  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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