Rare cancer responds unusually well to new treatment: results from the NETTER-1 trial
Prof Philippe Ruszniewski - Paris Diderot University, Paris, France
You have focussed in on mid-gut neuroendocrine tumours, why?
Because there is a great unmet need for mid-gut neuroendocrine tumours. The other, let’s say, common primary is pancreas but here we have quite a number of compounds or even of chemotherapy compounds which are active; this is not the case for mid-gut tumours. So we don’t really have many treatment possibilities in our patients. The second reason is that mid-gut tumours are the most frequent ones.
You’ve been trying a guided missile approach to treating them, a directed drug, you’re using something called 177 Lutetium DOTATATE, can you tell me about that agent?
Lutetium DOTATATE, what is it? It’s the combination of octreotide, for which a receptor exists on the cell surface, a chelator and the radionuclide which is lutetium-177. So the drug is injected by intravenous route, reaches the tumour cell, is bound to the tumour cell membrane due to the presence of the receptor, is then internalised into the tumour cell and then induces damage to the DNA inside the cell.
And mid-gut NETs are something of an unmet need, medically, are they not?
Exactly, I agree. Chemo is not effective; targeted therapies have limited efficacy, although we just learned in this meeting that everolimus could be also useful in this respect. So we are left without many treatment options.
So what did you do in the study?
We compared in a prospective fashion in two groups of 115 patients each Lu-TATE and high dosage of octreotide which means 60mg every 28 days. To be complete I would say that in the Lu-TATE arm 30mg of octreotide were also given to the patient in order to control their symptoms. We compared the effect of those treatments on progression free survival.
Now, you have got a big signal in terms of progression free survival and also overall response rate. What did you get?
So a huge difference between the two arms since PFS was 8.4 months in the octreotide 60mg arm and not reached in the Lu-TATE arm. Hazard ratio was 0.21, this means that the risk reduction in progression was almost 80%, which is huge.
What does this imply clinically, then, for the treatment now of these tumours?
I think that this implies that first of all, let’s say, approval from European and American authorities should probably be the next step and this will be, in my view, a turn in patient treatment. Because now this would definitely be a treatment that could be used in all progressive patients with mid-gut metastatic mets. So this is definitely big news.
What is the clinical take-home message for cancer doctors right now?
I think that the take-home message is that you can prevent tumour progression and we didn’t discuss tumour shrinkage but we saw that in 20% of the cases. So you can delay tumour progression, obtain tumour shrinkage in 20% of your patients and maybe, but this is too early to be said now, increase overall survival, up to now we just have a trend but the study is still ongoing, in your mid-gut patients with neuroendocrine tumours.
We’ve also been hearing about a broader category of NETs, results using everolimus. Do you think your new therapy could now form a whole new vanguard of approaches for neuroendocrine tumours?
I’m convinced that this is the case. I think that now, in this very important meeting we heard that two treatment options become available for those patients - everolimus and PRT or Lu-TATE. So I think that we should remember that these patients have very long life expectancy, even at the metastatic stage and I would say that it’s not a question of choice because should I give this one, should I give that one? No, I think that our patients do receive all the available treatments during the course of their disease. So should we start with everolimus, should we start with PRT? I think in each individual case there are arguments to select one option or the other but I think that we are very happy to have two options, by the way.