Capivasertib
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | DRUG-CAPIVASERTIB |
|---|---|
| Тип | Препарат |
| Синоніми | AZD5363TruqapКапівасертиб |
| Статус | переглянуто 2026-04-27 | очікує клінічного підпису |
| Хвороби | DIS-BREAST |
| Джерела | SRC-ESMO-BREAST-METASTATIC-2024 SRC-NCCN-BREAST-2025 |
Дані про препарат
| Клас | Pan-AKT1/2/3 ATP-competitive inhibitor |
|---|---|
| Механізм дії | Potent ATP-competitive small-molecule inhibitor of all three AKT serine/threonine kinase isoforms (AKT1, AKT2, AKT3) within the PI3K-AKT-mTOR signaling pathway. Suppresses downstream phosphorylation of effector substrates (FOXO, GSK3, TSC2, MDM2, 4EBP1 via mTORC1), reducing proliferation and survival signaling and partially reversing endocrine-therapy resistance in HR+ breast cancer driven by PI3K-pathway alterations. Tumors with activating PIK3CA / AKT1 mutations or PTEN loss (~40-50% of HR+/ HER2- mBC after CDK4/6i) are enriched for response. Pivotal evidence CAPItello-291 (HR+/HER2- mBC after AI ± CDK4/6i): capivasertib + fulvestrant vs placebo + fulvestrant — overall mPFS 7.2 vs 3.6 mo HR 0.60; in PIK3CA/AKT1/PTEN-altered subgroup mPFS 7.3 vs 3.1 mo HR 0.50. FDA approval Nov 2023 (mutation-restricted). |
| Типове дозування | 400 mg PO BID on an intermittent 4-days-on / 3-days-off schedule (e.g., Days 1-4, 8-11, 15-18, 22-25 of a 28-day cycle), in combination with fulvestrant 500 mg IM Days 1, 15 of cycle 1 then Day 1 of subsequent 28-day cycles. The intermittent schedule is critical — it was empirically optimized in phase-1 for tolerability (continuous dosing produced unacceptable hyperglycemia and diarrhea). Dose level -1 = 320 mg BID; -2 = 200 mg BID; permanent discontinuation if recurrent G3-4 at -2. Hold for severe hyperglycemia (FBG ≥250 / random ≥500 / DKA), severe diarrhea (G3-4), severe rash (G3-4 / SCAR), severe hepatotoxicity. No formal renal adjustment for CrCl ≥30; avoid in severe hepatic impairment. |
| Зареєстровано в Україні | False |
| Відшкодовується НСЗУ | False |
| Остання перевірка для України | 2026-04-27 |
Нотатки
Eligibility gate: PIK3CA / AKT1 activating mutation OR PTEN loss-of- function alteration on tumor or ctDNA NGS (FDA companion diagnostic FoundationOne CDx). The 4-on / 3-off intermittent schedule is critical — continuous dosing in phase-1 was intolerable. Hyperglycemia is the signal AE — substantially less than alpelisib (~70% vs ~17% any-grade) but still requires baseline HbA1c, fasting glucose, patient education on symptoms, and proactive metformin / insulin if pre-existing dysglycemia. Diarrhea management: prophylactic loperamide as needed (not routine); dietary modification; hold + resume at lower dose for G3+. Rash: dermatology referral early; topical / oral steroid taper; hold for G3. Baseline workup: HbA1c, fasting glucose, CMP, LFTs, lipid panel, pregnancy test, ECG, dermatologic exam. Monitor fasting glucose weekly first 4 weeks then with each cycle, HbA1c q3 months, LFTs q2 wk first 8 wk then monthly. UA access via EAP / self-pay; not on НСЗУ.
Де використовується
Regimens
REG-CAPIVASERTIB-FULVESTRANT-BREAST- Capivasertib + fulvestrant (HR+/HER2- PIK3CA/AKT1/PTEN-altered metastatic post-AI/CDK4/6i)