Capivasertib regimen represents potential new treatment option for advanced breast cancer
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SAN ANTONIO — The addition of capivasertib to fulvestrant significantly extended PFS among patients with hormone receptor-positive, HER2-negative breast cancer, according to results presented at San Antonio Breast Cancer Symposium.
Capivasertib (AZD5363, AstraZeneca) — an investigational AKT inhibitor — also appeared safe and exhibited a manageable toxicity profile, findings of the randomized phase 3 CAPItello-291 trial showed.
Background and methods
“AKT activation is very frequent in many hormone receptor-positive, HER2-negative advanced breast cancers through genetic alterations in the pathway, but they can also occur in cancers without genetic alterations,” Nicholas C. Turner, MD, PhD, professor in the department of molecular oncology at The Institute of Cancer Research in London and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said during a press conference. “AKT signaling is also implicated in the development of resistance to endocrine therapy, so capivasertib was developed as a potent selective inhibitor of all three AKT isoforms.”
As Healio previously reported, the CAPItello-291 trial included 708 men and women with histologically confirmed hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer.
All patients experienced disease progression or recurrence during or after aromatase inhibitor therapy, with or without a cyclin-dependent kinase 4/6 inhibitor.
All patients received up to one line of chemotherapy for advanced disease.
Researchers randomly assigned patients 1:1 to fulvestrant plus either capivasertib (n = 355) or placebo (n = 353).
PFS by investigator assessment in the overall study population and in the subgroup of those with AKT pathway-altered tumors served as dual primary endpoints. Secondary endpoints included OS and objective response rate.
Findings
Researchers reported longer median PFS among patients assigned capivasertib than placebo (7.2 months vs. 3.6 months; HR = 0.6; 95% CI, 0.51-0.71).
Results also showed a higher ORR in the capivasertib group (22.9% vs. 12.2%).
Among the 41% of patients with AKT pathway tumor mutations, researchers reported longer median PFS (7.3 months vs. 3.1 months; adjusted HR = 0.5; 95% CI, 0.38-0.65) and a higher ORR (28.8% vs. 9.7%) among those treated with capivasertib.
An exploratory analysis among those with nonaltered tumors showed longer median PFS with capivasertib (7.2 months vs. 3.7 months; HR = 0.7; 95% CI, 0.56-0.88).
“A prespecified subgroup analysis also showed capivasertib had a consistent effect across all prespecified subgroups, including those with or without liver metastases, as well as those with or without prior treatment with CDK 4/6 inhibitors,” Turner said.
Follow-up for OS is ongoing.
Common grade 3 or higher adverse events with capivasertib included rash (12.1%), diarrhea (9.3%) and hyperglycemia (2.3%).
A higher percentage of patients assigned capivasertib discontinued treatment (13% vs. 2.3%).
Implications
“The safety profile of capivasertib plus fulvestrant appears consistent with that previously reported, with a relatively low discontinuation rate due to adverse events,” Turner said. “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.”
Perspective
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Turner N, et al. Abstract GS3-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022.
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