FDA Approves Capivasertib/Fulvestrant for Advanced/Metastatic, HR+, HER2- Breast Cancer


The FDA has approved capivasertib plus fulvestrant to treat patients with locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations.

The FDA has approved capivasertib (Truqap) along with fulvestrant to treat adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with 1 or more PIK3CA/AKT1/PTEN-alterations.

The indication is specific to patients who have already progressed beyond at least 1 prior endocrine-based regimen in the metastatic setting or those who have recurred within 12 months of completing adjuvant therapy.

Of note, the FDA also approved FoundationOne®CDx assay as a companion diagnostic device. This will help identify patients who are eligible for this treatment approach.

Efficacy Data

Findings from the randomized, double-blind, placebo-controlled, multicenter CAPItello-291 trial (NCT04305496) supported this approval. CAPitello-291 included 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer. A total of 289 participants also had tumors with PIK3CA/AKT1/PTEN-alterations.

In the population of patients with PIK3CA/AKT1/PTEN-altered tumors, the median progression-free survival was 7.3 months (95% CI, 5.5-9.0) with the investigational treatment and 3.1 months (95% CI, 2.0-3.7) in the placebo-based group, resulting in a 50% reduction in the risk of disease progression or death (HR, 0.50; 95% CI, 0.38-0.65; P < .0001).

In the exploratory analysis of patients whose tumors did not harbor aPIK3CA/AKT1/PTEN alteration (n = 313), the reduction in risk of disease progression or death was 21% (HR, 0.79; 95% CI, 0.61-1.02), signaling to investigators 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 CAPItello-291 trial

All patients in the trial had already undergone treatment with an aromatase inhibitor and patients were able to have undergone up to 2 prior lines of endocrine therapy and 1 prior line of chemotherapy for locally advanced or metastatic disease.

Patients in the trial were randomly assigned 1:1 to receive either capivasertib at a 400-mg dose, or placebo, for 4 days, followed by 3 days off, for a 28-day treatment cycle. All patients received a 500-mg dose of intramuscular fulvestrant on days 1 and 15 of cycle 1, and then every 28 days thereafter. Patients were able to continue this regimen until either disease progression or unacceptable toxicity.

Progression-free survival, both in the overall population as well as those with tumor mutations, was the major efficacy outcome.

Safety Profile

In the trial, the most reported adverse events 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.


FDA approves capivasertib with fulvestrant for breast cancer. FDA. News release. November 16, 2023. Accessed November 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-capivasertib-fulvestrant-breast-cancer

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