Capivasertib Plus Fulvestrant Prolonged PFS in HR-Positive, HER2-Negative Advanced Breast Cancer

According to results of a double-blind, phase 3 study, the addition of capivasertib to fulvestrant significantly prolonged progression-free survival (PFS) compared to fulvestrant alone among patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer who had experienced disease progression after treatment with an aromatase inhibitor, with or without the addition of a CDK4/6 inhibitor. 

As Nicholas C. Turner, MD, PhD, Royal Marsden Hospital, London, United Kingdom, and coauthors stated, “AKT pathway activation is implicated in endocrine-therapy resistance” but, “data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with [HR]–positive advanced breast cancer are limited.”

In this trial, 708 patients were randomized on a 1-to-1 basis to receive either capivasertib plus fulvestrant or fulvestrant plus placebo. Of the total study population, 289 patients harbored AKT pathway alterations, and 489 patients had received prior treatment with a CDK 4/6 inhibitor for advanced breast cancer. The dual primary end points were investigator-assessed PFS among patients in the overall population and among patients who harbored AKT pathway alterations. Additionally, researchers assessed safety. 

Among all patients, the median PFS in the capivasertib arm was 7.2 months vs 3.6 months in the placebo arm (hazard ratio [HR] for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P < .001). Among patients who harbored AKT pathway alterations, median PFS was 7.3 months in the capivasertib arm and 3.1 months in the placebo arm (HR, 0.50; 95% CI, 0.38 to 0.65; P < .001). 

The most frequent grade ≥3 or higher adverse events included rash (12.1%, capivasertib; 0.3%, placebo) and diarrhea (9.3%, capivasertib; 0.3%, placebo). Adverse events that led to treatment discontinuation occurred in 13% of patients in the capivasertib arm and 2.3% of patients in the placebo arm.

Dr Turner et al concluded, “Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone” among patients in this population.

Source: 
Turner NC, Oliveira M, Howell SJ, et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. Published online June 1, 2023. doi:10.1056/NEJMoa2214131