KEY TAKEAWAYS
- The Phase 2 FAKTION trial tested capivasertib in AI-resistant ER+/HER2- advanced breast cancer patients.
- The main goal was to assess PFS between fulvestrant with capivasertib and placebo.
- Targeted next-generation sequencing and digital droplet PCR were used to detect PIK3CA/AKT1/PTEN pathway changes.
- Capivasertib improved OS and PFS in PA tumor patients but not PNA tumor patients.
- Capivasertib may assist PA and PNA tumor patients in Phase 3 studies like CAPItello-291.
Progression-free survival (PFS) was significantly improved in patients with aromatase inhibitor (AI) resistant ER+/HER2 advanced breast cancer when fulvestrant plus capivasertib was compared to fulvestrant plus placebo in the Phase 2 FAKTION study (NCT01992952).
Patients with activating mutations in PIK3CA (E542K, E545K, H1047R, or H1047L) or PTEN protein null were not excluded from the examination of the PFS advantage associated with capivasertib. Completed analyses of biomarkers for overall survival (OS) are now being reported. Tissue and plasma samples were sent to targeted next-generation sequencing (NGS) using the Foundation One CDx and GuardantOMNI assays for improved analysis. Any mutation in PIK3CA (exons 1,4,7,9,20), AKT1 (E17K only), or PTEN (inactivating) was considered a “pathway altered” (PA) mutation. Samples not undergoing targeted NGS testing were analyzed by digital droplet PCR (ddPCR) for PIK3CA and, later, by ddPCR for AKT1 in tissue. The ddPCR results agreed with the NGS results for 97% of the mutations. In the intention to treat (ITT) population, 108 OS occurrences were documented in January 2022, representing 77% maturity. In the capivasertib group (n = 69), the median OS was 29.3 months, while in the placebo group (n = 71), the median OS was 23.4 months (mo) (HR 0.66, 95% CI 0.45-0.97; p = 0.035).
76 people were labeled PA in the improved biomarker analysis, up from 59 in the baseline study. Overall survival (OS) in the PA group was 39.0 months for those on capivasertib versus 20.0 months for those taking a placebo (HR 0.46, 95% CI: 0.27-0.79; p = 0.005). Median overall survival (OS) was not significantly different between the capivasertib and placebo arms among the pathway non-altered (PNA) group (HR 0.86, 95% CI: 0.49-1.52; p = 0.60).
Capivasertib had an advantage over the placebo in the updated PFS analysis in the ITT sample (median 10.3 vs 4.8 months, HR 0.56, 95% CI: 0.38-0.81; p = 0.002). Compared to the placebo group, patients in the capivasertib arm had a significantly longer PFS (12.8 months versus 4.6 months; HR 0.44, 95% CI: 0.26-0.72; p = 0.003). Median progression-free survival (PFS) for patients with PNA was 7.7 months in the capivasertib arm and 4.9 months in the placebo arm (HR 0.70, 95% CI: 0.40-1.25; p = 0.23). An updated look at the data from the FAKTION trial reveals a substantial increase in OS among the ITT population. Capivasertib’s benefit in progression-free survival (PFS) and overall survival (OS) may be concentrated in patients with PIK3CA/AKT1/PTEN pathway-altered tumors, according to an expanded subgroup analysis; however, the ongoing Phase 3 CAPItello-291 study, in which patients with PA and PNA tumors have been enrolled, will shed more light on this question.
Source:https://meetings.asco.org/abstracts-presentations/208056
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT01992952
Robert Hugh Jones, Angela Claire Casbard, Margherita Carucci, Kate Ingarfield-Herbert, Rachel Butler, Sian Morgan, Magdalena Meissner, Catherine Jane Bale, Pavel Bezecny, Sarah Moon, Chris Twelves, Ramachandran Venkitaraman, Simon Waters, Elza De Bruin, Gaia Schiavon, Andrew Foxley, Sacha Jon Howell/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 40, 2022 (suppl 16; abstr 1005)
DOI10.1200/JCO.2022.40.16_suppl.1005
