ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago
Interview with Professor Chris Twelves (St James's Hospital, Leeds, UK)
New agent eribulin prolongs survival in metastatic breast cancer
Tell us all about your important talk at ASCO.
It is an important study and it’s the sort of study that I think most oncologists would be delighted to have the opportunity to present, because I’ve been coming to ASCO for 20 or more years, and there have really only been a handful of drugs in that time that have shown prolonged survival in metastatic breast cancer. Eribulin, a new drug, has completed a phase-III study which has achieved just that, a significant prolongation of survival for women with heavily pre-treated breast cancer.
Women who had had everything such as hormones, cytotoxics and antibodies?
They’d had hormonal therapy. They could have had trastuzumab or herceptin. They had had up to five lines of previous chemotherapy, so these were very heavily pre-treated women where there really aren’t any current standard approved options. So, these are women who are really up against it.
How did you get involved?
I was involved in the earlier developments of this drug and when there were discussions with the regulatory authorities after phase-II studies which showed clear evidence of activity. We were required to do a phase-III study, and it was in designing the study that I got involved, principally in the design and the discussions around the treatment of physicians’ choice aspect, which was the control arm.
Tell us about the control arm.
It came out of the discussions with the regulatory authorities, EMA, where they said they would like or needed a randomised study. We said there isn’t an appropriate control arm. They agreed but said, go away and find one. So, we opted to really make a positive out of this. Rather than mandate a single control arm that would not have matched for most oncologists, which they might offer their women normally, we allowed them to choose any monotherapy. It could be a chemotherapy, could be biological, could be endocrine therapy or it could be best supportive care. But, for each individual woman, the oncologist, as he randomised the patients, was able to say what that standard treatment or routine treatment would be. So, it’s an unusual situation where the treatment of physicians’ choice was actually tailored to the individual patient who received the control arm.
How did it work in practice?
It worked in practice very successfully because we saw a two-and-a-half month prolongation of overall survival with eribulin. For the oncologist and indeed for the patients, we’re able to put that in the context of real-life practice and everyday practice, so that we can say or present this to our colleagues as a two-and-a-half month benefit over what they might expect using one of the other routine chemotherapies that they might currently be offering women.
What is next for eribulin?
Well, the regulatory wheels have started to turn and the approval process will now begin. At the same time, there are already important other studies ongoing. There’s a randomised study in women who were pre-treated but less heavily pre-treated, where they were randomised in a more conventional manner to receive either capecitabine – which would be a standard treatment – or to receive eribulin. So, that study has completed accrual and should be available in around 18 months, and there are combination studies. In Leeds, we’re doing a combination study actually looking at combining capecitabine with eribulin. So, it’s moving on several different fronts.
After that, what is further up the line?
Well, that would be to speculate at the moment, but it’s certainly very noticeable as we present these data to the investigators, their enthusiasm at ways to take eribulin earlier into the course of the treatment of this disease.
What’s the pre-clinical spectrum like in chemotherapy-resistant lines?
There’s good activity and I think the most encouraging activity is that the agent does have activity in taxol-resistant lines. So, in cell lines with beta-Tubulin mutations, eribulin retains activity. So, this helps emphasise that this isn’t simply a taxane. It isn’t a taxane at all. It’s a completely different structure. It targets the microtubules, but it does so in a different way to the alkaloids, a different way to the taxanes or the epothilones, and the fact that it has activity against resistant lines and that it also causes less neurotoxicity than paclitaxel preclinically really mark it out as being quite distinct from the current tubulin-targeted agents.
Do you think it might be an anti-metastatic agent?
That’s an interesting concept because at the back of our mind with a number of the agents that work via the microtubules is this potential to have anti-metastatic activity. So, I think it certainly would have that potential as well, yes.
