We’ve been hearing from you this morning about fulvestrant. This has got a bit of a history to it because it’s actually a very potent drug, it was as good as Tamoxifen in treating breast cancer. Can you give me that back story first because I want to ask you about your new studies?
It was initially introduced at a dose of 250mg and was shown in the second line setting to be equivalent to anastrozole and in the first line setting to be similar to Tamoxifen. But subsequent to that the dose was increased to 500mg and there has been a study of the second line setting of 500mg, it was called the CONFIRM study, and that showed that, compared to 250mg, the new dose, 500mg, gave a time to progression advantage, treatment on the disease, but that also translated into a survival advantage.
First of all why was it not eagerly taken up at 250mg because it was as good as anastrozole and Tamoxifen?
It was as good as or similar to the other drugs but no better than and it was more expensive because it was new drug and therefore it tended to be used subsequent to the other drugs, as against the 500mg dose, as I said, which we’ve confirmed was better than its comparator.
So what have you done now?
The FIRST study shows that the fulvestrant 500mg dose is better than the standard arm which is the third generation aromatase inhibitor anastrozole. It’s better in terms of improved survival, it shows its unique mode of action, and also that the 500mg dose gives you greater control of that pathway, the oestrogen receptor.
In broad figures could you put some numbers on the survival benefit and how much superior it is to the alternatives?
30% more women are alive at the end of the study period in the fulvestrant group than in the anastrozole group. That means that the overall survival is significantly longer; the median survival is 54 months as against the anastrozole arm which is 5.5 months shorter. So this is a significant advance. To give that some context too, all of the subgroups, whether it was age, site of disease, prior systemic therapy, all of the subgroups show the same benefit. To put that in a wider context of where we are today, when I started looking after women with metastatic breast cancer 20-30 years ago the average survival was 24 months, we are now reporting 54 months. So this is a new step up in that whole process that we’ve seen over the last 20 years of improving the survival and the outcome of women with metastatic breast cancer. As I said, we see 30% less deaths during the study period on the new drug.
So what do you think clinically this could imply for doctors right now?
I think that you have to see it in a wider context again which is, as I said before, the CONFIRM data shows a time to progression and a survival difference in terms of second line. Fulvestrant 500mg is the only drug I know that has shown a benefit in both second and first line therapy for TTP and survival. Having said that, the study is still a phase II trial, it’s not a phase III trial which most people would want to see before they say it’s completely practice changing. So there’s a difference here between, say, funders and what an individual doctor and a physician might decide. If you’re a funder and you’re paying tax dollars or tax pounds you would want to be sure that you’re spending that health money on something that is definitely shown to be more beneficial. Funders will understandably wait to see the phase III trial, and there is a phase III trial that has been performed and we’re waiting for the results and we can talk about that in a moment, but that’s what the funders will do correctly. Individual doctors and physicians may have a discussion and somebody may say, “Well, I can afford to pay for this and I want to have something like this,” and they may make a different decision individually, based on what their own circumstances are.
Now the size of the study and the level of the statistical significance, what are they and just the broad figures for overall survival and time to progression?
Yes, the current study is a phase II 200 patient study and what it shows is the hazard ratio is 0.7, so it’s a 30% reduction in deaths in the fulvestrant treated arm. Now, as I say, it’s 54 months that you have in the fulvestrant arm. In the phase III trial, which is called the FALCON trial, that is a 450 patient study, so much larger, powered more and that has finished recruitment so the study is done in that sense. What we’re now waiting to see is the events happen so that we can report on that.
Do you have a provisional recommendation to make to doctors, then, at this point?
From a standard of care position that still remains an aromatase inhibitor. As I say, individual doctors and physicians will look at the data and make their own decision based on what that situation is. For example, somebody who maybe has Alzheimer’s or forgetfulness and doesn’t take tablets well, the doctor may say, “I’m going to in this individual case now use fulvestrant 500mg.” But I think as a standard of care that is still the AI, still the non-steroidal AI, but individual doctors will talk to their patients and come to individual decisions.
And this is an injection.
This is an injection.
So does that count against it, do you think, in the routine use?
I don’t think it does because the one thing here is that you know you get compliance and that’s what I was talking about. For example, in a situation with somebody who might have Alzheimer’s you can be sure you’re getting compliance so I think that there are advantages to that.
A quick bottom line message for doctors is what?
We have seen with this study that the AIs can be beaten in terms of their effect and their control of cancer, breast cancer in the metastatic setting, that’s the first thing. The second message to doctors is that as a standard of care we are still waiting for the phase III trial to come through but that they will make their own decision based on the patient, the particular individual patient, they have and the data that they’ve viewed.