Introduction
Truqap (capivasertib) is an oral small molecule kinase inhibitor developed by AstraZeneca for the treatment of hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer. It represents a novel therapeutic approach targeting the AKT pathway, which is frequently dysregulated in cancer cells.
Mechanism of Action
Truqap is a potent, selective adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1, AKT2, and AKT3). It works by binding to the kinase domain of AKT, preventing phosphorylation and subsequent activation of downstream signaling pathways. By inhibiting the PI3K/AKT/mTOR pathway—a critical regulator of cell proliferation, survival, and metabolism—Truqap induces cell cycle arrest and promotes apoptosis in cancer cells with pathway activation.
Indications
Truqap is indicated in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN alterations who have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.
Dosage and Administration
Recommended dosage: 400 mg orally twice daily (approximately 12 hours apart) for 4 days followed by 3 days off each week Administration: Take with or without food at approximately the same times each day Dose modifications: Required for management of adverse reactions including hyperglycemia, diarrhea, cutaneous reactions, and other toxicities Special populations:- Renal impairment: No dosage adjustment recommended for mild to moderate impairment
- Hepatic impairment: Not recommended in patients with severe hepatic impairment
- Geriatric patients: No specific dosage adjustment required
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of 2-4 hours; high-fat meal increases exposure by approximately 1.4-fold Distribution: Apparent volume of distribution ~220 L; protein binding >99% Metabolism: Primarily via CYP3A4 with minor contributions from UGT1A1, UGT2B7, and sulfation Elimination: Mean half-life ~7 hours; primarily fecal excretion (69%) with renal excretion accounting for 19% Special populations: No clinically significant differences based on age, sex, race, or body weightContraindications
- History of serious hypersensitivity reactions to capivasertib or any component of the formulation
- Concurrent use with strong CYP3A inducers
- Patients with type 1 diabetes or diabetic ketoacidosis
Warnings and Precautions
Hyperglycemia: May cause severe hyperglycemia; monitor blood glucose levels and initiate antihyperglycemic agents as needed Diarrhea: May cause severe diarrhea leading to dehydration and electrolyte imbalances; initiate antidiarrheal therapy promptly Cutaneous reactions: Serious skin reactions including erythema multiforme reported Embryo-fetal toxicity: Can cause fetal harm; advise patients of reproductive potential of potential risk Photosensitivity: Increased risk of sunburn; advise sun protection measuresDrug Interactions
Strong CYP3A inhibitors: Avoid concomitant use (e.g., ketoconazole, itraconazole) Strong CYP3A inducers: Contraindicated (e.g., rifampin, carbamazepine) Moderate CYP3A inducers: Consider alternative agents or monitor for reduced efficacy CYP3A substrates: May increase concentrations of sensitive CYP3A substrates P-glycoprotein substrates: May increase concentrations of P-gp substratesAdverse Effects
Most common (≥20%): Diarrhea, rash, nausea, fatigue, vomiting, decreased appetite, increased glucose, increased creatinine, anemia, leukopenia, lymphopenia Serious adverse reactions: Severe hyperglycemia, severe diarrhea, cutaneous reactions, pneumonitis Laboratory abnormalities: Hyperglycemia, increased creatinine, anemia, lymphopenia, thrombocytopeniaMonitoring Parameters
- Blood glucose levels at baseline and regularly during treatment
- Renal function (serum creatinine) at baseline and periodically
- Complete blood count with differential at baseline and periodically
- Liver function tests at baseline and periodically
- Signs and symptoms of diarrhea, cutaneous reactions, and hyperglycemia
- Pregnancy testing in patients of reproductive potential
Patient Education
- Take exactly as prescribed with consistent timing
- Report any severe diarrhea, skin changes, or symptoms of hyperglycemia (excessive thirst, urination)
- Use effective contraception during treatment and for 1 month after final dose
- Limit sun exposure and use protective measures including sunscreen
- Do not consume grapefruit or grapefruit juice during treatment
- Inform all healthcare providers about Truqap use before starting new medications
- Do not interrupt or stop treatment without medical advice
References
1. FDA Prescribing Information: Truqap (capivasertib) 2. Turner NC, et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2023;388(22):2058-2070 3. Schmid P, et al. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: The PAKT trial. J Clin Oncol. 2020;38(5):423-433 4. ClinicalTrials.gov: CAPItello-291 study (NCT04305496) 5. Saura C, et al. Capivasertib plus fulvestrant versus placebo plus fulvestrant in postmenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer. ESMO 2022 Abstract LBA17
This monograph is for educational purposes only. Healthcare professionals should consult the full prescribing information and clinical guidelines before prescribing Truqap.