Meghana Kesireddy, MBBS, assistant professor, Department of Oncology & Hematology, The University of Nebraska Medical Center, discusses the pending FDA approval of the AKT inhibitor capivasertib plus the selective estrogen receptor degrader fulvestrant (Faslodex) in patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

granted priority review to capivasertib plus fulvestrant

 for patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer whose disease has progressed or recurred on or after endocrine-based therapy. This designation was based on data from the phase 3 CAPItello-291 trial (NCT04305496), in which patients who received capivasertib plus fulvestrant achieved a median progression-free survival (PFS) of 7.2 months vs 3.6 months with placebo plus fulvestrant (hazard ratio, 0.60; 95% CI, 0.51-0.71; 

The PFS benefit with capivasertib vs placebo was observed in the overall population in CAPItello-291, which included a subgroup of patients with AKT pathway alterations in their tumors, Kesireddy says. It is unclear whether the FDA will approve capivasertib plus fulvestrant in all patients with HR-positive, HER2-negative locally advanced or metastatic disease, or only in those with diseaseharboring alterations in the AKT pathway, Kesireddy notes. Although the combination generated a PFS benefit vs placebo plus fulvestrant in patients without known AKT pathway alterations, 15.0% of patients in the overall population had unknown AKT pathway alteration status but were evaluated as part of the AKT-nonaltered population, Kesireddy explains. Thus, it is unclear whether the PFS benefit observed with capivasertib in the AKT-nonaltered population reflects a general benefit with the agent in all comers, or a benefit in patients with AKT pathway alterations alone, Kesireddy emphasizes. 

The population in which capivasertib plus fulvestrant will be indicated in if granted FDA approval remains unclear. However, this combination if approved has the potential to become the standard of care for patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer whose disease has progressed after their first line of endocrine therapy, joining elacestrant (Orserdu), which is 

approved for patients in this population with

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Meghana Kesireddy, MBBS, discusses the pending FDA approval of the AKT inhibitor capivasertib plus the selective estrogen receptor degrader fulvestrant in patients with hormone receptor–positive, HER2-negative breast cancer.

Meghana Kesireddy, MBBS

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Dr Kesireddy on the Future Use of Capivasertib Plus Fulvestrant in HR+/HER2– Breast Cancer