"The emerging role of capivasertib in breast cancer"

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Over 50% of breast tumors have genetic alterations in the phosphatidylinositol 3-kinase (PI3K) pathway.
• While PI3K and mTOR inhibitors are approved, AKT inhibitors represent a novel therapeutic strategy for breast cancer.

Purpose of the Study:

• To evaluate the efficacy and safety of capivasertib, a novel pan-AKT kinase inhibitor, in breast cancer.
• To explore capivasertib's potential in combination therapies for hormone receptor-positive, HER2-negative breast cancer.

Main Methods:

• Preclinical studies in breast cancer cell lines.
• Phase I/II clinical trials evaluating capivasertib as monotherapy and in combination with paclitaxel and fulvestrant.
• Ongoing Phase III trials (CAPItello-291, -292, -290) assessing combinations with fulvestrant, palbociclib, and paclitaxel.

Main Results:

• Preclinical studies showed capivasertib efficacy in PIK3CA or MTOR-altered breast cancer.
• Phase I/II trials indicated enhanced efficacy with capivasertib combined with paclitaxel or fulvestrant in HR+, HER2- breast cancer.
• The recommended Phase II dose was 480 mg twice daily on a 4-days-on, 3-days-off schedule. Common Grade ≥3 adverse events included hyperglycemia, diarrhea, and rash.

Conclusions:

• Capivasertib demonstrates preclinical and early clinical activity in breast cancer, especially in tumors with PI3K pathway alterations.
• Combination therapies with capivasertib show promise in HR+, HER2- breast cancer.
• Further Phase III trials are crucial to establish the definitive therapeutic role of capivasertib in various breast cancer settings.