These results were presented at the 2022 ASCO Annual Meeting and published in The Lancet Oncology.1,2
The phase 2 FAKTION trial (ClinicalTrials.gov Identifier: NCT01992952) enrolled postmenopausal women with ER-positive, HER2-negative, metastatic or locally advanced inoperable breast cancer who had relapsed or progressed on an AI.
Patients were randomly assigned to receive fulvestrant with either capivasertib (n=69) or placebo (n=71) until disease progression, unacceptable toxicity, loss to follow-up, or consent withdrawal.
In the primary analysis of FAKTION, there was a significant improvement in PFS with capivasertib, but the OS data were immature.3 At that time, PI3K/AKT/PTEN pathway alterations did not appear to impact the effects of treatment.
In the current analysis, the researchers expanded biomarker profiling to include next-generation sequencing assays. The team hypothesized that this would more accurately identify PI3K/AKT/PTEN pathway status.
For the current analysis, the median follow-up was 58.5 months in the capivasertib arm and 62.3 months in the placebo arm.
The median PFS was 10.3 months in the capivasertib arm and 4.8 months in the placebo arm (adjusted hazard ratio [aHR], 0.56; 95% CI, 0.38–0.81; P =.002). The median OS was 29.3 months and 23.4 months, respectively (aHR, 0.66; 95% CI 0.45–0.97; P =.035).
The expanded biomarker analysis revealed PI3K/AKT/PTEN pathway alterations in tumors that were originally classified as non-altered. Overall, 76 patients had PI3K/AKT/PTEN pathway-altered tumors, and 64 did not.
In the group with PI3K/AKT/PTEN pathway-altered tumors, the median PFS was 12.8 months with capivasertib and 4.6 months with placebo (aHR, 0.44; 95% CI, 0.26-0.72; P =.0014). The median OS was 38.9 months and 20.0 months, respectively (aHR, 0.46; 95% CI, 0.27–0.79; P =.005).
In the group with non-altered tumors, the median PFS was 7.7 months with capivasertib and 4.9 months with placebo (aHR, 0.70; 95% CI, 0.40-1.25; P =.23). The median OS was 26.0 months and 25.2 months, respectively (aHR, 0.86; 95% CI, 0.49–1.52; P =.60).
There were no new safety signals in the updated analysis, according to study author Robert Hugh Jones, PhD, of Cardiff University in the United Kingdom.
He concluded that the FAKTION data support further development of capivasertib. The capivasertib-fulvestrant combination is currently under investigation in the phase 3 CAPItello-291 trial (ClinicalTrials.gov Identifier: NCT04305496).
Disclosures: This research was partly supported by AstraZeneca, Cenduit LLC, and Labcorp (formerly Covance). Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Jones RH, Casbard AC, Carucci M, et al. Fulvestrant plus capivasertib versus fulvestrant plus placebo after relapse or progression on an aromatase inhibitor in metastatic, estrogen receptor–positive breast cancer (FAKTION): Overall survival and updated progression-free survival data with enhanced biomarker analysis. Presented at ASCO 2022; June 3-7, 2022. Abstract 1005.
- 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. Lancet Oncol. Published online June 4, 2022. doi:https://doi.org/10.1016/S1470-2045(22)00284-4
- Jones RH, Casbard A, Carucci M, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): A multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020; 21: 345-57. doi:https://doi.org/10.1016/S1470-2045(19)30817-4