Dr Advani on the Role of Capivasertib Plus Fulvestrant in HR+/HER2– Breast Cancer

Pooja Advani, MBBS, MD, hematologist/oncologist, Mayo Clinic Comprehensive Cancer Center, discusses the potential utilization of capivasertib (Truqap) plus fulvestrant (Faslodex) in select hormone receptor (HR)–positive, HER2-negative breast cancer.

On November 2023, the FDA approved the AKT inhibitor capivasertib in combination with fulvestrant for patients with HR–positive, HER2-negative metastatic or locally advanced disease and 1 or more mutations in the PIK3/AKT/PTEN pathway, as detected by an FDA approved companion test, Advani begins. Patients were also required to have experienced disease progression after at least 1 endocrine-based regimen in the metastatic setting, or recurrence on or within 12 months of completing adjuvant therapy.

The regulatory decision was based on data from the phase 3 CAPItello-291 trial (NCT04305496), Advani states. This registrational multicenter trial enrolled over 700 patients in the metastatic setting, she details. The study encompassed the patient population that received the capivasertib and fulvestrant combination, but a specific focus was placed on the pathway-altered population, Advani adds.

Results showed that the combination produced a median progression-free survival of 7.3 months vs 3.1 months (95% CI, 2.0-3.7) for those treated with placebo plus fulvestrant (n = 134; HR 0.50; 95% CI, 0.38, 0.65; P < .0001). Although the combination demonstrated significant benefits in both the overall patient population and in those with the specified alterations, the current regulatory approval is specifically granted for patients with these identified alterations, Advani clarifies. This represents a noteworthy development and an additional therapeutic option for this subgroup of patients, Advani explains.

Notably, the observed rate of hyperglycemia with the combination was lower compared with the PIK3CA inhibitor alpelisib (Piqray) in combination with fulvestrant. This reduced incidence is particularly important for the oncology community, as managing this adverse effect can often present a substantial challenge in clinical practice. Overall, the favorable safety profile of capivasertib plus fulvestrant further enhances the appeal of this combination as a viable and well-tolerated treatment option for patients in the metastatic setting, especially those with PIK3/AKT/PTEN pathway alterations.