Capivasertib Gets FDA Approval for Treatment of HR-Positive, HER2-Negative Breast Cancer

By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY


On November 16, 2023, the U.S. Food and Drug Administration approved capivasertib (Truqap, AstraZeneca Pharmaceuticals) in combination with Fulvestrant for adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations, as detected by the FDA-approved FoundationOne®CDx assay. This approval comes after these patients have shown progression post at least one endocrine-based regimen in the metastatic setting or recurrence within 12 months of finalizing adjuvant therapy.


Study ID: NCT04305496


Approval was based on CAPItello-291, a randomized, double-blind, placebo-controlled, multicenter trial that included 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer, of which 289 patients had tumors with PIK3CA/AKT1/PTEN-alterations. Capivasertib was given orally at a dosage of 400 mg twice daily for 4 days, followed by 3 days off treatment each week over a 28-day treatment cycle until disease progression or unacceptable toxicity.


Efficacy was established on the investigator-assessed progression-free survival (PFS) in the overall population and in the population of patients whose tumors had PIK3CA/AKT1/PTEN-alterations.


Results of the study showed a statistically significant difference in PFS 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 and 3.1 months (95% CI: 2.0, 3.7) in the placebo-fulvestrant group (HR: 0.50 [95% CI: 0.38, 0.65] p-value< 0.0001). In overall population (N=355), patients treated with capivasertib had a PFS of 7.2 months (95% CI, 5.5-7.4), nearly double the 3.6 months (95% CI, 2.8-3.7) in those given a placebo with fulvestrant (HR, 0.60; 95% CI, 0.51-0.71; P < .001). However, patients without PIK3CA/AKT1/PTEN genetic alterations showed a slight but not significant improvement in PFS. This indicates that the extended PFS was mainly due to benefits in patients with these specific genetic changes.


The most common side effects of the medication were diarrhea, skin reactions, increased random glucose, decreased lymphocytes, decreased hemoglobin, increased fasting glucose, nausea, fatigue, decreased leukocytes, increased triglycerides, decreased neutrophils, increased creatinine, vomiting and stomatitis.


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