medwireNews: The addition of the AKT inhibitor capivasertib to fulvestrant significantly prolongs the progression-free survival (PFS) of people with hormone receptor-positive, HER2-negative advanced breast cancer that is resistant aromatase inhibitors (AIs), indicate the results of CAPItello-291.
Presenting the findings at the 2022 San Antonio Breast Cancer Symposium in Texas, USA, Nicholas Turner (Royal Marsden Hospital, London, UK) noted that the PFS benefit was observed both in the overall trial population and the subset with alterations in the AKT pathway.
He explained that the phase 2 FAKTION study, previously reported by medwireNews, showed that supplementing fulvestrant with capivasertib significantly improved PFS and overall survival (OS) in patients with AI-resistant advanced breast cancer, “with a more pronounced benefit in pathway altered tumours.”
The current phase 3 trial included 708 men and pre- or postmenopausal women who had progressed on an AI and received no more than two prior lines of endocrine therapy and no more than one line of chemotherapy for advanced disease. Prior CDK4/6 inhibitor therapy was permitted and around 70% of patients had previously taken this class of drugs.
Turner reported that the co-primary endpoint of investigator-assessed PFS in the overall population was significantly longer for the patients who were randomly assigned to receive capivasertib 400 mg twice daily on a 4 days on, 3 days off schedule rather than placebo, where both were given alongside fulvestrant 500 mg on days 1 and 15 of the first cycle, then every 4 weeks.
He pointed out that the Kaplan–Meier curves “separate early and stay separated for the duration of follow-up.”
The median PFS duration was 7.2 months with capivasertib and 3.6 months with placebo, equating to a significant 40% reduction in the risk for progression or death with the addition of the AKT inhibitor.
The other primary endpoint of the trial – PFS in the 289 participants with AKT pathway alterations (most commonly PIK3CA mutations) – also significantly favored the capivasertib group, at a median of 7.3 months compared with 3.1 months in the placebo group. The risk for progression or death was halved with capivasertib use in this subset of patients.
An exploratory analysis restricted to the 419 patients without AKT pathway alterations showed a significant benefit of capivasertib in this population also, with median PFS times of 7.2 and 3.7 months in the capivasertib and placebo arms, respectively, and a risk reduction of 30%.
Adding capivasertib to fulvestrant also boosted the objective response rate relative to placebo plus fulvestrant in the overall (22.9 vs 12.2%) and AKT-altered (28.8 vs 9.7%) populations.
The overall survival data were immature at the time of analysis and follow-up is ongoing, said the presenter.
He added that the safety profile of capivasertib plus fulvestrant “appears consistent with that previously reported, with a relatively low discontinuation rate due to adverse events [AEs].”
In the overall trial population, the most common AE in capivasertib-treated patients was diarrhea, with events of grade 1 and 2 in 63.1% and grade 3 in 9.3%. By contrast, the respective rates in placebo-treated patients were 19.7% and 0.3%.
A total of 13.0% of patients in the capivasertib group discontinued any study treatment due to AEs compared with 2.3% of those in the placebo group, and a respective 1.1% and 0.3% of AEs were fatal.
“Capivasertib plus fulvestrant has the potential to be a future treatment option” for patients with hormone receptor-positive advanced breast cancer who have progressed on an endocrine-based regimen, concluded the investigator.
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