Revised Overall Survival and Progression-Free Survival Data from the FAKTION Study: Capivasertib + Fulvestrant in Metastatic, ER-Positive Breast Cancer

The phase 2 FAKTION study showed that fulvestrant plus capivasertib had a significantly longer progression-free survival (PFS) rate than fulvestrant plus placebo in patients with aromatase inhibitor–resistant estrogen receptor (ER)-positive/HER2-negative advanced breast cancer. The combination’s PFS advantage benefited a broader patient population than those with mutations in PIK3CA or PTEN protein null. Overall survival (OS) data with improved biomarker analyses can now be reported.

Available tissue and plasma samples were analyzed using targeted next-generation sequencing (NGS) with FoundationOne CDx and GuardantOMNI assays. Any activating mutation in PIK3CA (exons 1, 4, 7, 9, 20) or AKT1 (E17K only) or inactivating mutations in PTEN were classified as pathway altered (PA). Moreover, previously reported digital droplet polymerase chain reaction (ddPCR) data for PIK3CA were used for samples not examined by targeted NGS. The similarity between ddPCR-identified mutations and subsequently performed NGS was 97%.

In January 2022, the intention-to-treat (ITT) population had reached 77% maturity for events in the OS analysis. The median OS in the capivasertib (n = 69) and placebo (n = 71) groups was 29.3 months versus 23.4 months, respectively (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.45-0.97; P = .035). A total of 76 participants were identified as PA in the improved biomarker analysis, compared with 59 in the original analysis. In the PA group, the capivasertib versus placebo arms had a 39.0 versus 20.0 months OS difference (HR, 0.46; 95% CI, 0.27-0.79; P = .005). Within the pathway nonaltered (PNA) group, the capivasertib versus placebo arms had a median OS of 26.0 months versus 25.2 months, respectively (HR, 0.86; 95% CI, 0.49-1.52; P = .60). The benefit of capivasertib versus placebo in the ITT population was maintained in the revised median PFS analysis (10.3 vs 4.8 months; HR, 0.56; 95% CI, 0.38-0.81; P = .002). PFS was significantly improved in the PA group compared with the updated biomarker subgroups: 12.8 months versus 4.6 months in the capivasertib versus placebo arms, respectively (HR, 0.44; 95% CI, 0.26-0.72; P = .001). In the PNA group, the capivasertib versus placebo arms had a median PFS of 7.7 versus 4.9 months (HR, 0.70; 95% CI, 0.40-1.25; P = .23).

In the ITT population, an updated review of the FAKTION trial data showed significant improvement in OS. Enhanced subgroup analysis revealed that patients harboring tumors with altered PIK3CA/AKT1/PTEN pathway signaling may benefit from capivasertib in both PFS and OS, but further information will come from the ongoing phase 3 CAPItello-291 trial, which is recruiting patients with both PA and PNA ER-positive/HER2-negative advanced breast cancers.


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. J Clin Oncol. 2022;40:16. Abstract 1005.

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