The treatment of advanced pancreatic neuroendocrine tumours (pNET)

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Published: 4 Nov 2010
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Prof Kjell Öberg - University Hospital, Uppsala, Sweden

Prof Kjell Öberg discusses the development of new biomarkers which allow early detection of pNET and identify patients who are at high risk of recurrence after surgery and speaks about the superiority of molecular imaging with PET scan over traditional imaging technologies. Prof Öberg explains how he would interpret conflicting scan results and talks about everolimus, sunitinib and pasireotide, three promising new drugs for the treatment of advanced pNET.

ESMO 2010

 

Professor Kjell Öberg - University Hospital, Uppsala, Sweden

 

The treatment of advanced pancreatic neuroendocrine tumours (pNET)

  

 

Professor Öberg, thank you very much indeed for coming to join us. This is a busy ESMO for you and you’ve been in the neuroendocrine tumour session and you’ve been talking about some very important organisational things – classification etc, but also about the new research tools that are coming through for diagnosis and also for treatment. What was the most important thing that you were getting over today at ESMO?

 

What I wanted to convey to the audience was that we had to use a new classification system because their survival is depending on the classification and also the selection of treatment. The other thing is that using these traditional imaging modalities - CT scans, ultrasound and MRIs – is not sufficient, you need more sophisticated methods and that is molecular imaging with PET scanning. One of the most recent PET scans are the gallium-68 octreotate, it’s also called the Poor Man’s PET because it’s using a generator to generate an isotope, not a cyclotron. It has higher sensitivity than octreoscan.

 

Another thing which was also a part of my talk was new biomarkers. We have the old chromogranin A but we are now working on new biomarkers for early detection and also recurrence after surgery.

 

Such as?

 

We have one called PNMA2 which is just about to be published and it can particularly reliably show the patients that have a risk of recurrence after surgery.

 

So better at finding recurrence than early detection?

 

Yes.

 

So the molecular imaging is very exciting, isn’t it? If you’ve got a patient with a hotspot on an octreoscan in the tail of the pancreas, negative MRI and negative CT, you do a gallium scan for that or is that overkill?

 

No, actually if I have a positive standard CT scan or MRI it’s sufficient for…

 

But if they’re negative but the octreoscan is positive?

 

But if they’re negative and the octreoscan is positive, I think I trust the octreoscan and send in the surgeon because he is doing inter-operative ultrasonography during the operation anyhow. So he can confirm that this is the lesion. But you must also confirm by biochemistry that chromogranin A has increased also.

 

So the biomarkers are exciting and the imaging should be becoming more standard and it should be easier for people to do this without a cyclotron, that’s what the message is. Treatment?

 

The treatment is really exciting just now because we have at least three new drugs around the corner. One is the everolimus mTOR inhibitor, or Afinitor is the trade name, and we now have three different randomised trials that have demonstrated a significant benefit in neuroendocrine tumours, both in pancreatic neuroendocrine tumours but also in mid-gut carcinoid tumours.

 

The other ones?

 

The other one is sunitinib, which is a tyrosine kinase inhibitor, not only blocking VGF but also PDGF and it has in pancreatic mets demonstrated a significant anti-tumour effect.

 

The third one is the other new somatostatin analogue, pasireotide, which can be used in patients resistant to standard somatostatin analogues, octreotide and lanreotide, giving a significant effect first of all on symptoms and on biomarkers but also on tumour size.

 

Pasireotide blocks four of the five receptors?

 

Four of the five receptors, yes.

 

And combinations of these?

 

Yes, combinations have been done with everolimus and octreotide showing additive effects. It has also been done with sunitinib but it’s not quite clear if there’s an additive effect. We can of course combine pasireotide with the new drugs as well but it’s not available at the moment for such testing. I have tested pasireotide with alpha interferon with dramatic effects on tumour size so there are things in the future that look very promising. Then, of course, radioactive treatment is also expanding - the PRRT, peptide radio receptor treatment with lutetium-177 and also yttrium-90.

 

Very busy, very exciting times for neuroendocrine tumours.

 

Yes, definitely and for the patient.

 

It’s much better news.

 

Yes.

 

Professor Öberg, thank you very much indeed.