Fulvestrant Plus Capivasertib Extends Survival in ER-Positive, HER2-Negative Breast Cancer

Fulvestrant plus capivasertib yielded consistently longer overall survival (OS) and progression free survival (PFS) among patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to a findings from a phase 2 study.

“Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported to improve progression-free survival in women with aromatase inhibitor-resistant [ER]-positive, HER2-negative advanced breast cancer,” wrote lead author Sasha Howell, PhD, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK, and coauthors,

The phase 2 FAKTION trial assessed 183 patients between March 16, 2015, and March 6, 2018, 140 of whom were randomized in a 1:1 ratio to receive  fulvestrant plus capivasertib (n = 69) or capivasertib and placebo (n = 71). Patients were treated until disease progression, unacceptable toxicity, loss to follow-up, or withdrawal of consent.

The primary trial end point was PFS in the intention-to-treat population. Secondary end points included OS and safety in the intention-to-treat population. Researchers also assessed the effect of tumor PI3K/AKT/PTEN pathway status using an expanded testing panel that included next-generation sequencing assays.

At a data cutoff of November 25, 2021, the median follow-up was 58.5 months in the capivasertib group and 62.3 months in the placebo group. Fulvestrant plus capivasertib yielded significantly prolonged PFS (10.3 months [95% confidence interval {CI}, 5 to 13.4 months]) vs placebo plus fulvestrant (4.8 months [95% CI, 3.1 to 7.9 months]). Median OS was 29.3 months (95% CI, 23.77 to 39) vs 23.4 months (95% CI, 18.7 to 32.7), respectively (hazard ratio [HR], 0.66; 95% CI, 0.45 to 0.97).

Expanded biomarker testing identified an expanded pathway-altered subgroup of 76 patients; 39 who received capivasertib vs 37 who received placebo. Among this population, the median PFS with capivasertib was 12.8 months (95% CI, 6.6 to 18.8) vs 4.6 months (95% CI, 2.8 to 7.9) with placebo (HR, 0.44; 95% CI, 0.26 to 0.72). Median OS was 38.9 months (95% CI, 23.3 to 50.7) vs 20 months (95% CI, 14·8 to 31·4), respectively (HR, 0.46; 95% CI, 0.27 to 0.79).

Researchers noted that there was no statistically significant differences in PFS or OS with capivasertib (n=30) vs placebo (n=34) in the expanded pathway non-altered subgroup.

“Updated FAKTION data showed that capivasertib addition to fulvestrant extends the survival of participants with aromatase inhibitor-resistant ER-positive, HER2-negative advanced breast cancer,” concluded Dr Howell and colleagues, adding, “the expanded biomarker results also suggest that genomic tumour profiling will be needed to accurately identify the approximately 50% of patients whose tumours carry relevant PI3K/AKT/PTEN pathway alterations and will most benefit from capivasertib.

Source:

Howell SJ, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lance Oncol. June 2022. doi:10.1016/S1470-2045(22)00284-4