You’ve been reporting on a phase II study and it’s looking at what you do for patients who fail standard therapy for cervical cancer. Can you tell me what you were trying to do in this study and why you needed to do the study?
We cure 70% of all patients in Europe either by surgery or chemo-radiotherapy but 30% either relapse or are seen at diagnosis with a disseminated disease. We have no really satisfactory treatment for these women who have a miserable time. With conventional chemotherapy our experience is only 20-30% have tumour shrinkage and the majority are dead, in fact virtually all are dead, within a year.
And why did you turn to this small molecule inhibitor of vascular endothelial growth factor receptor?
Two reasons: firstly work done in Manchester showed that a higher angiogenesis and/or a high level of VEGFR was a bad prognostic factor for radiotherapy; it wasn’t known for chemotherapy but radiotherapy. This was the group of women particularly who relapsed after radiotherapy. AstraZeneca came along with this tyrosine kinase inhibitor, cediranib, and it looked favourable for blocking VEGFR. It’s quite a powerful inhibitor of both VEGFR receptors 1, 2 and 3.
So what did you do in the study?
It was a simple study. We took a well-known chemotherapeutic combination, carboplatinum paclitaxel, that surprisingly hadn’t been reported being used in cervix cancer, and we give this to both arms of the study. One arm got cediranib orally, 20mg once daily, the other arm an identical placebo. We followed the patients up until either relapse or death. The ones who got cediranib continued indefinitely; the ones on the placebo also continued indefinitely.
OK, so tell me what the outcome was.
We got statistically significant results with just 69 patients. The first thing is that we had a superior response rate. Our control arm did rather better than we expected with a 42% tumour shrinkage by RECIST criteria but the cediranib arm had a 66% response rate. There was a modest difference in progression free survival, 35 weeks for cediranib, 30 weeks for the placebo, but interestingly there is a tail of long-term survivors. In total 9 out of the original 69 are alive at more than two years without tumour progression.
So I think I heard these patients were alive at one year and then none of them died after that.
That’s right. The survival curve is flat.
So what’s happening, do you think?
We don’t know. The next thing we’re going to do is an individual patient analysis by the fall in VEGFR levels but, more than that, Caroline Dive’s laboratory in Manchester are going to look at other receptors to see what else we were blocking.
What could potentially be the clinical application of this work with this small molecule TKI inhibitor?
What we might learn is why do some of these women survive a long time. We may get the actual receptors that were blocked and this will help us for next year’s trial by saying what we need is something that’s going to block x, y and z. Because obviously this blockade is terribly important.
How would you sum up what this means, though, for clinicians.
I think we’ve got a completely new window of opportunity which we didn’t have before. Old chemotherapy, basically, was pretty useless. What we’ve actually got is a window of opportunity to design completely novel treatments for this group of patients. It’s worth saying that cervix cancer is uncommon in Europe but worldwide it’s the second most common cancer in women.
And the very brief take home message would be what?
Targeting the blood vessels is very important in the treatment of cervix cancer.