Capivasertib — Drug Monograph

Capivasertib (Truqap) — PIK3CA / AKT1 / PTEN Breast Cancer Overview

Capivasertib (Truqap) is a first-in-class, ATP-competitive pan-AKT inhibitor for HR-positive, HER2-negative advanced breast cancer harboring PIK3CA, AKT1, or PTEN alterations detected by an FDA-approved test. AKT is the central node of the PI3K/AKT/PTEN pathway, and activating PIK3CA or AKT1 mutations — or PTEN loss — drive proliferation and endocrine resistance. Because on-target AKT2 inhibition causes predictable hyperglycemia, capivasertib uses a distinct intermittent oral schedule (4 days on, 3 days off). This monograph covers capivasertib indications, its dosing schedule, PIK3CA/AKT1/PTEN biomarker selection, and blood-glucose monitoring.

Indications (FDA / NCCN)

• HR-positive, HER2-negative advanced breast cancer with PIK3CA/AKT1/PTEN alterations, + fulvestrant, after progression on endocrine therapy (CAPItello-291)
• Requires a PIK3CA, AKT1, or PTEN alteration confirmed by an FDA-approved test
• Given after progression on at least one endocrine-based regimen

Dosing

• 400 mg orally twice daily (~12 h apart)
• Intermittent schedule: 4 days on, 3 days off each 7-day cycle
• Combined with fulvestrant 500 mg IM (Days 1, 15, 29, then monthly)
• Swallow tablets whole; take with or without food

Monitoring

• Fasting plasma glucose (FPG) and HbA1c at baseline
• FPG at Week 2, Week 4, then monthly; hold for fasting glucose >250 mg/dL
• Diarrhea — start loperamide at the first loose stool
• Cutaneous reactions — early topical corticosteroids; watch for SJS / erythema multiforme

Brand names: Truqap

Drug class: Other

Mechanism of Action

Capivasertib is a first-in-class, potent, selective ATP-competitive pan-AKT kinase inhibitor that blocks all three AKT isoforms (AKT1, AKT2, AKT3). AKT is the central node of the PI3K/AKT/PTEN signaling axis; activating alterations in PIK3CA or AKT1, or loss-of-function alterations in PTEN, drive constitutive AKT activation that promotes tumor cell proliferation, survival, and endocrine resistance in HR-positive breast cancer. By inhibiting AKT, capivasertib suppresses downstream mTORC1 and FOXO-mediated signaling. Because AKT2 is a key mediator of insulin signaling, on-target pan-AKT…

FDA Indications

• HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations (detected by an FDA-approved test), following progression on at least one endocrine-based regimen, in combination with fulvestrant (CAPItello-291)

Common Side Effects

• Hyperglycemia (fasting plasma glucose elevation; on-target AKT2 effect — most characteristic toxicity)
• Diarrhea (frequent; can be severe — proactive loperamide at first loose stool)
• Rash / maculopapular rash (cutaneous reactions common)
• Nausea
• Fatigue
• Vomiting
• Stomatitis
• Decreased appetite
• Anemia
• Lymphopenia

Clinical Pearl

Capivasertib's 4-days-on/3-days-off intermittent schedule is a deliberate design feature, not a convenience — the drug-free interval lets on-target AKT2-mediated hyperglycemia recover between pulses while preserving anti-tumor activity. Screen FPG and HbA1c at baseline and check FPG at Week 2, Week 4, then monthly; hold for fasting glucose >250 mg/dL. Unlike alpelisib (which shares the glycemic axis via upstream PI3Kalpha), capivasertib's toxicity is driven directly at AKT. Treat diarrhea…

Related Therapies & Mechanisms

• Elacestrant (Orserdu) — Other · Breast
• Eribulin (Halaven) — Other · Breast
• Everolimus (Afinitor) — Other · Breast
• Adagrasib (Krazati) — Other