Robert Hugh Jones, MD, PhD, on Breast Cancer: Updated Overall Survival Data on Fulvestrant Plus Capivasertib

So the FAKTION trial is a randomized phase two trial that compares the activity of a hormone therapy called Fulvestrant plus capivasertib, which is an AKT inhibitor, compared to Fulvestrant and placebo in patients with oestrogen-receptor-positive, HER2-negative breast cancer, which is incurable. So patients with metastatic disease. and what we did in the first instance is we randomized patients one to one to get either Fulvestrant plus capivasertib or Fulvestrant plus placebo. And in the first instance, we looked at progression-free survival in the intention to treat population. This was reported around three years ago, and it showed that patients who got the capivasertib had a survival or progression-free survival of around about 10.3 months compared to 4.8 months, if you got the Fulvestrant plus placebo. At that time, we did some limited biomarker analysis to see were the patients who had an activated pathway with PI3-kinase mutations were more likely to get benefit from those than those patients that didn't have an activated pathway. At that time, there was no difference between the two groups. So the advantage you couldn't distinguish which patient groups were going to get the most advantage. What we've now done is we've waited some time and done further analysis. So what we are looking at now is overall survival and looking at a more extensive biomarker analysis. And what we found most importantly was patients not only experienced longer time to control their cancer in the capivasertib group, but they had a longer overall survival. So within unselected patient groups that was around about six months, it was 29 months compared with 23 months. But when we did the biomarker analysis, we identified a greater number of patients that had what we call an altered pathway. So around about 54% of patients had an altered pathway. And when we looked at those patients, they were the ones that got the most benefit. So in terms of overall survival, patients with an activated pathway had around about 39 months worth of life. Whereas patients who had an activated pathway, but got placebo only had around 20 months when we looked at the patients that didn't have an activated pathway, there was very little difference between the two groups. So there was no particular benefit in getting the extra capivasertib drug. And what that means is that we can now select patients out who are most likely to benefit from this new treatment. It is a phase two study. So on its own, it won't change practice, but we have right behind it, a phase three study called CAPItello, and that will be looking at a much larger group of patients. And what we can then see is whether this large group of patients get a similar benefit. The other thing to mention is that because FAKTION was recruiting a number of years ago, patients weren't getting CDK4/6 inhibitors before entry into the study standard practice has now changed. And therefore the phase three study that's following on will look at that group of patients that are getting CDK4/6 inhibitors. And therefore it'll be more representative of real life data. We hope the phase three study repeats the incremental benefits that we've seen in the phase two. And that in turn could lead to a change in practice.