On November 16, 2023, capivasertib (Truqap) was approved for use with fulvestrant for patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations, following disease progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.1 The U.S. Food and Drug Administration also approved the FoundationOneCDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with capivasertib with fulvestrant.
OF NOTE
Capivasertib has warnings/precautions for hyperglycemia, diarrhea, cutaneous adverse reactions, and embryofetal toxicity.Supporting Efficacy Data
Approval was based on the double-blind CAPItello-291 trial (ClinicalTrials.gov identifier NCT04305496), in which 708 patients, including 289 with PIK3CA/AKT1/PTEN alterations, were randomly assigned to receive capivasertib at 400 mg or placebo twice daily for 4 days followed by 3 days off treatment each week every 28 days; both groups received fulvestrant at 500 mg intramuscularly on cycle 1 days 1 and 15 and then every 28 days thereafter. Treatment continued until disease progression or unacceptable toxicity. All patients were required to have disease progression on aromatase inhibitor–based treatment.
A significant improvement in progression-free survival was observed in the capivasertib group in the overall population and among patients with PIK3CA/AKT1/PTEN alteration. Among patients with PIK3CA/AKT1/PTEN alteration, median progression-free survival was 7.3 months (95% confidence interval [CI] = 5.5–9.0 months) in the capivasertib group vs 3.1 months (95% CI = 2.0–3.7 months) in the control group (hazard ratio = 0.50, 95% CI = 0.38–0.65, P < .0001). Among 313 patients without such alterations, the hazard ratio was 0.79 (95% CI = 0.61–1.02), indicating the difference in the overall population was primarily attributed to the results in the population with PIK3CA/AKT1/PTEN alteration.
How It Is Used
The recommended capivasertib dose is 400 mg twice daily for 4 days followed by 3 off days until disease progression or unacceptable toxicity. Dosage modifications, including dose reduction, for adverse reactions are provided in the product labeling. Concomitant use with strong CYP3A inhibitors (eg, clarithromycin, erythromycin, fluconazole) and strong and moderate CYP3A inducers (eg, glucocorticoids, rifampin, phenobarbital) should be avoided.
Safety Profile
Safety data are from 155 patients in the capivasertib group and 133 patients in the control group in CAPItello-291 who had PIK3CA/AKT1/PTEN alteration. The most common adverse events of any grade in the capivasertib group occurring at an incidence at least 3% higher than in the control group were diarrhea (77% vs 19%), cutaneous adverse reactions (56% vs 16%), fatigue (38% vs 27%), nausea (35% vs 14%), and stomatitis (25% vs 5%). The most common grade 3 or 4 adverse events in the capivasertib group included cutaneous adverse events (15%), diarrhea (12%), and renal injury (2.6%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (11%) and increased random glucose (9%).
Serious adverse events occurred in 18% of patients in the capivasertib group, most commonly cutaneous adverse events (3.9%), diarrhea (2.6%), and pneumonia (2.6%). Adverse events led to discontinuation of capivasertib in 10% of patients, most commonly cutaneous adverse events (6%). Fatal adverse events occurred in 1.3%, including sepsis (0.6%) and acute myocardial infarction (0.6%).
Capivasertib has warnings/precautions for hyperglycemia, diarrhea, cutaneous adverse reactions, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving capivasertib.
REFERENCE
1. Truqap (capivasertib) tablets, for oral use, prescribing information, AstraZeneca, November 2023. Available at https://www.azpicentral.com/pi.html?product=truqap. Accessed June 18, 2024.
