We presented in a poster the first interim analysis of the BYLieve study. This is a phase II single arm trial, essentially, with two different treatments so it’s not randomised it’s actually selected by prior treatment. Really, what the goal of the study is is to evaluate the efficacy and toxicity of the PI3 kinase alpha-specific inhibitor alpelisib, now approved in combination with fulvestrant for the treatment of metastatic hormone receptor positive breast cancer with a known PI3 kinase mutation based on the results of SOLAR-1.
We wanted to evaluate in this particular trial what the efficacy and toxicity was of alpelisib in combination with endocrine therapy in patients who have received prior CDK4/6 inhibitors. In SOLAR-1 only about 3% of patients were exposed to prior CDK4/6 inhibitors so this is really a need for the oncologists and patients to understand efficacy and toxicity in that population. Because we knew that this would be a more heavily pre-treated population we allowed patients to receive either fulvestrant or letrozole in the trial population. So you could have received either of those hormone therapies before and have progressed on them but it couldn’t have been your last hormone treatment. So you had to switch from your last hormone treatment – if that was fulvestrant you received letrozole, if that was letrozole you received fulvestrant.
So it’s a very mixed population of patients and we don’t yet have the data on which patients had already progressed on the endocrine therapy they were on in BYLieve. The patients all had to have documented evidence of a PI3 kinase mutation and then they were placed on alpelisib in combination with that chosen endocrine agent.
We actually just did the first interim analysis and will have more data for ASCO in 2020. But what we were able to show was response rates that were very reasonable and similar to what we would have expected from the data from SOLAR-1 which was quite nice because it does suggest, again very early, even in a patient population who are clearly higher risk and more endocrine resistant, that the PI3 kinase inhibitor maintains its efficacy. So that was exciting.
We don’t really have progression free survival data yet because it’s too early. We know that people stayed on therapy for a reasonable amount of time, so that’s good. In terms of toxicity we saw data very similar to what was in SOLAR-1 but a much lower discontinuation rate. Interestingly, I think this is largely because if you know a drug works you keep people on it. They also weren’t randomised, which is helpful. The awareness of how to manage the toxicity of alpelisib is continuing to improve over time. So what we know about management of the toxicity is that the key thing to understand is, one, rash and using antihistamines preventively appears to have a big effect. In fact, the label for alpelisib notes that patients who took antihistamines in the trial, although it wasn’t a requirement, had less rash. So that’s good. In terms of hyperglycaemia it is a real toxicity and a class effect for PI3 kinase inhibitors. So what we are working on is actually having good guidelines about managing hyperglycaemia in our patients. We know that patients who come in with borderline glucose control are more likely to get that toxicity. Thankfully it doesn’t involve much in the way of serious toxicities, which is encouraging. Then diarrhoea is usually manageable pretty easily.
There are actually a number of groups that are working on different ways to try and manage the hyperglycaemia, including things like the keto diet or low carbohydrates. So it’s going to be really interesting to see how that plays out but this is clearly a very effective class of drugs. Alpelisib is the first approved PI3 kinase inhibitor, so an exciting step forwards towards personalised and precision medicine for breast cancer.