Capivasertib Doubles PFS in Some Breast Cancers

Area of Science:

• Oncology
• Pharmacology

Background:

• Hormone receptor-positive (HR+), HER2-negative breast cancer is the most common subtype.
• Acquired resistance to endocrine therapy and CDK4/6 inhibitors remains a significant clinical challenge.
• Targeting the AKT pathway is a potential strategy for overcoming resistance.

Purpose of the Study:

• To evaluate the efficacy and safety of capivasertib plus fulvestrant versus placebo plus fulvestrant in patients with advanced HR+, HER2-negative breast cancer with specific genetic alterations.
• To assess the impact of this combination therapy on progression-free survival (PFS).

Main Methods:

• Phase III, randomized, double-blind, placebo-controlled clinical trial (CAPItello-291).
• Patients with locally advanced or metastatic HR+, HER2-negative breast cancer resistant to prior endocrine therapy and CDK4/6 inhibitors were enrolled.
• Treatment arms included fulvestrant plus capivasertib or fulvestrant plus placebo.

Main Results:

• The combination of fulvestrant and capivasertib more than doubled progression-free survival compared to fulvestrant alone.
• Significant improvements in PFS were observed across patient subgroups, including those with PIK3CA/AKT1/PTEN alterations.
• Safety profiles were consistent with known side effects of the agents.

Conclusions:

• Capivasertib in combination with fulvestrant represents a potential new treatment option for patients with advanced HR+, HER2-negative breast cancer who have progressed on or after CDK4/6 inhibitors and endocrine therapy.
• Targeting the AKT pathway offers a viable strategy to overcome endocrine resistance in breast cancer.