Addition of Capivasertib to Fulvestrant Improved PFS Across All Key AKT Pathway Alterations Among Patients With HR-Positive, HER2-Negative Breast Cancer

According to an exploratory analysis of the CAPItello-291 trial, the benefit to progression-free survival (PFS) seen with the addition of capivasertib to fulvestrant was consistent among patients with alterations in all 3 key genes within the AKT pathway.

The phase 3 CAPItello-291 trial evaluated the addition of capivasertib, a potent, selective pan-AKT inhibitor, to fulvestrant among patients with aromatase inhibitor-resistant, hormone receptor-positive, HER2-negative advanced breast cancer. There were 708 patients randomized on a 1-to-1 basis to receive fulvestrant plus either placebo or capivasertib. It has been previously reported that capivasertib plus fulvestrant improved the PFS versus placebo plus fulvestrant (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.51 to 0.71; P < .001). This PFS benefit was observed among patients with detectable ATK pathway alterations and those without.

Of the enrolled patients, 289 had AKT pathway-altered tumors (capivasertib arm, n = 155; placebo arm, n = 134). A majority of patients (n = 272) had only 1 detectable alteration: PIK3CA, PTEN, or AKT1. There were 13 patients with co-occurring PIK3CA and PTEN alterations, and 4 with co-occurring PIK3CA and ATK1 alterations. The benefit to PFS seen with capivasertib was consistent across all alterations. The HR for patients with only PIK3CA alterations was 0.51, with only PTEN alterations was 0.43, and with only AKT1 alterations was 0.51. The safety profile among the patients with the AKT-altered pathway tumors was consistent with the overall population.

Study authors concluded, “compared with fulvestrant alone, the addition of capivasertib to fulvestrant provided a consistent PFS benefit across alterations in all 3 key genes with the AKT pathway in patients with HR-positive, HER2-negative [advanced breast cancer].”

Source:

Howell S, Rugo H, Oliveira O, et al. Capivasertib and fulvestrant for patients with aromatase inhibitor-resistant HR positive/HER2-negative advanced breast cancer: Exploratory analysis of PFS by AKT pathway gene from the phase 3 CAPItello-291 trial. Presented at San Antonio Breast Cancer Symposium; Dec 5-10, 2023; San Antonio, Texas. PS17-03