General Information

Truqap (capivasertib) is a kinase inhibitor of AKT1, AKT2 and AKT3.

Truqap is specifically indicated for use in combination with fulvestrant for the treatment of 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-alteration as detected by an FDA-approved test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.

Dosing/Administration

• Truqap is supplied as tablets for oral administration.
• Select patients for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer with Truqa, based on the presence of one or more of the following genetic alterations in tumor tissue: PIK3CA/AKT1/PTEN
• Evaluate fasting blood glucose (FG) and hemoglobin A1C (HbA1C) prior to starting Truqap and at regular intervals during treatment
• The recommended dosage of Truqa, in combination with fulvestrant, is 400 mg orally twice daily (approximately 12 hours apart) with or without food, for 4 days followed by 3 days off. Continue Truqap until disease progression or unacceptable toxicity.
• Swallow Truqap tablets whole. Do not chew, crush, or split tablets prior to swallowing. Do not take tablets that are broken, cracked, or otherwise not intact.
•  If a patient misses a dose within 4 hours of the scheduled time, instruct the patient to take the missed dose. If a patient misses a dose more than 4 hours of the scheduled time, instruct the patient to skip the dose and take the next dose at its usual scheduled time.
•  If a patient vomits a dose, instruct the patient not to take an additional dose and take the next dose at its usual scheduled time.
•  Refer to the fulvestrant Full Prescribing Information for recommended fulvestrant dosing information

Mechanism of Action

Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA). In vitro, capivasertib reduced growth of breast cancer cell lines including those with relevant PIK3CA or AKT1 mutations or PTEN alteration. In vivo, capivasertib alone and in combination with fulvestrant inhibited tumor growth of mouse xenograft models including estrogen receptor positive breast cancer models with alterations in PIK3CA, AKT1, and PTEN.

Side Effects

Adverse effects associated with the use of Truqap may include, but are not limited to, the following:

• 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
• stomatitis

Clinical Trial Results

The FDA approval of Truqap was based on the phase 3 CAPItello-291 trial. The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial had dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumors have qualifying alterations in the PI3K/AKT/PTEN pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumors had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor.

In the trial, Truqap in combination with fulvestrant reduced the risk of disease progression or death by 50% versus fulvestrant alone in patients with tumors harboring PI3K/AKT/PTEN pathway biomarker alterations (median progression-free survival (PFS) 7.3 versus 3.1 months).