TRUQAP 200 mg

Indications

• Breast cancer with PIK3CA mutations
• Breast cancer with AKT1 mutations
• Breast cancer with PTEN alterations

Dosage

Children: Refer to the BNF for Children for

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Capivasertib inhibits the phosphorylation of downstream substrates of the AKT signaling pathway. The activation of AKT in tumors is often due to upstream signaling pathway activation, mutations in AKT1, loss of PTEN function, and alterations in PIK3CA. This inhibition effectively reduces the proliferation and survival of cancer cells that depend on these pathways.

Pharmacodynamics

In vitro studies have demonstrated that capivasertib reduces the growth of breast cancer cell lines, particularly those harboring PIK3CA or AKT1 mutations, or PTEN alterations. In vivo, it has shown efficacy in inhibiting tumor growth in mouse xenograft models of estrogen receptor-positive breast cancer, especially in cases with relevant genetic alterations. The specific exposure-response relationship and the time course for the pharmacodynamic effects of capivasertib remain to be fully characterized; however, relationships have been noted for side effects such as diarrhea, rash, and hyperglycemia at various dose levels.

Pharmacokinetics

The pharmacokinetics of capivasertib have not been fully elucidated in the provided data. However, it is known that its dosing can lead to increased QTc intervals, although a mean increase greater than 20 ms was not observed at the recommended dosage. Further pharmacokinetic details would typically include absorption, distribution, metabolism, and excretion profiles which are essential for understanding the drug's behavior in the body.

Adverse effects

• diarrhea
• rash
• hyperglycemia
• QT interval prolongation

Precautions

• Monitor for signs of diarrhea, rash, and hyperglycemia during treatment
• Assess QTc interval periodically
• Use caution in patients with a history of cardiac conditions

Pregnancy

There is insufficient data on the use of capivasertib in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether capivasertib is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets

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).

Pharmacodynamics

In vitro, capivasertib reduced the 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. The exposure-response relationship and time course of pharmacodynamic response for the effectiveness of capivasertib has not been fully characterized. Exposure-response relationships were observed for diarrhea (CTCAE Grade 2 to 4), rash (CTCAE Grade 2 to 4), and hyperglycemia (CTCAE Grades 3 or 4) at doses of 80 to 800 mg (0.2 to 2 times the approved recommended dosage). At the recommended capivasertib dose, a mean increase in the QTc interval > 20 ms was not observed.