Comparison of Capivasertib Plus Fulvestrant Versus Fulvestrant Alone in Advanced Breast Cancer

By: Anna Fanelli
Posted: Monday, July 10, 2023

The phase III randomized CAPItello-291 trial, reported in The New England Journal of Medicine, studied the efficacy and safety of the AKT pathway inhibitor capivasertib plus the estrogen receptor antagonist fulvestrant in the treatment of patients with hormone receptor–positive, HER2-negative advanced breast cancer. Nicholas C. Turner, MD, PhD, of the Royal Marsden Hospital and Institute of Cancer Research, London, and colleagues found that capivasertib plus fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor.

“Exploratory analyses in the AKT pathway–nonaltered population showed that capivasertib has activity beyond AKT pathway–altered tumors,” the study authors noted.

A total of 708 patients participated in this double blind, placebo-controlled trial. Of them, 289 had AKT pathway alterations, and 489 had received a CDK4/6 inhibitor previously for advanced breast cancer.

In the overall population, the median progression-free survival was 7.2 months in the capivasertib/fulvestrant group, compared with 3.6 months in the placebo/fulvestrant group. In the AKT pathway–altered population, the median progression-free survival was 7.3 months with capivasertib/fulvestrant, compared with 3.1 months with placebo/fulvestrant.

The most frequent adverse events reported in patients receiving the capivasertib/fulvestrant combination were rash and diarrhea. Adverse events leading to discontinuation of treatment were reported in 13% of the patients receiving capivasertib and in 2.3% of those receiving placebo.

Of note, in this trial, an intermittent administration schedule was used for capivasertib; the goal was to maximize AKT inhibition and optimize the therapeutic window. According to the investigators, that might be the reason for the low incidence of hyperglycemia reported with capivasertib.

Disclosure: For full disclosures of the study authors, visit www.nejm.org.

The New England Journal of Medicine

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