Medical Information

Capasertib is a new AKT kinase inhibitor, which plays an anti-tumor role by targeting the inhibition of PI3K/AKT/mTOR signaling pathway. At present, clinical research is mainly carried out for HR positive/HER2 negative advanced breast cancer. Its unique intermittent administration scheme can balance efficacy and safety.

1. Basic Information

(1) Common name: Kapasetinib Capivasertib

(2) R&D code: AZD5363

(3) Target characteristics: Selective inhibition of AKT1/2/3 subtypes, IC50 value of approximately 3nM

2. Mechanism of action

(1) Pathway inhibition: Blocking PI3K/AKT/mTOR signaling to overcome endocrine therapy resistance

(2) Cellular effects: induce G1 phase arrest and apoptosis, inhibit tumor cell proliferation and survival

(3) Synergism: Combination with fluoxetine can enhance the sensitivity of ER positive breast cancer cells

3 Indications

(1) Main indications: treatment of HR+/HER2 advanced breast cancer combined with fluoxetine (recognized by FDA as breakthrough therapy)

(2) Extended research: AKT1/PIK3CA mutant solid tumors (prostate cancer, endometrial cancer, etc.)

4 Usage and Dosage

(1) Standard protocol: 400mg orally twice a day (4 days of medication/3 days of discontinuation)

(2) Dose adjustment: can be reduced to 320mg or 200mg according to toxicity grading

(3) Medication precautions: Swallow the entire tablet and avoid combination with potent CYP3A4 inhibitors

5 Adverse Reactions

(1) Common reactions: diarrhea (58%), rash (39%), nausea (35%)

(2) Hematotoxicity: Neutropenia (28%), Anemia (22%)

(3) Special reactions: hyperglycemia (requiring monitoring), QT interval prolongation (baseline electrocardiogram examination)

6 Clinical data

(1) CAPItello-291 study: median PFS 7.2 months vs 3.6 months (control group)

(2) Objective response rate: ORR of AKT pathway mutation patients reaches 22%

(3) Survival benefits: trend of overall survival extension (mature data to be released)