ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago
Interview with Professor George Demetri (Harvard Medical School, USA)
Alk mutation related non-small cell lung cancer
Welcome to ecancer TV at ASCO. You have been very busy over the last couple of days and I don’t suppose it’s going to get any easier today. Thank you very much for giving us a couple of minutes.
Thanks for inviting me.
So what have you been picking up in the corridors? What’s really interesting?
This is an incredible year that’s forming the foundation for the next level of advances, I would say. We’ve come to ASCO expecting by now terrific data in certain areas and we realise that we’re going to be starting to nip off cancer as a problem every 5,000 patient group at a time, in the world, not in a country. So this year’s big news, of course, was all about the ALK mutations in non-small cell lung cancer; something that was just discovered about three years ago and has now been already translated into a very exciting therapy – a potential therapy with extraordinary activity in non-small cell lung cancer.
In phase I.
In phase I and also in a certain type of sarcoma. I would also say that, as someone who really believes that the rare diseases will point the way for the common diseases, there is this rare form of sarcoma known as inflammatory myofibroblastic tumour where the young people, typically aged less than 25, will have the same ALK problem and they’ve already had extraordinary responses in the phase I study. So what wasn’t discussed much is that, just like in the early days of Imatinib where we then did a basket study where anybody with the relevant Imatinib targets like PDGF receptor could go into a study even if they did not have CML or GIST. We’re going to do something very similar with ALK because there may be other diseases where ALK is disregulated and certainly we know it is in this form of sarcoma.
So the story keeps repeating itself one other type of kinase inhibitor at a time. Just like Sunitinib – why would the same drug hit renal cell cancer and GIST, two different targets? Sunitinib was also a very big disappointment in the breast cancer world because it really is not something that met its targets for a successful breast cancer therapy.
There were a couple of combination studies?
A couple of combination studies which were negative but that’s important because it also shows it’s not so simple – we really need targets that are tolerable and we really need to be smart about the way we design our studies. I think some of the most exciting things that came out were some of the combinations we’re starting to see. José Baselga’s group in Barcelona did a spectacular presentation on the combination of an mTOR inhibitor with the IGF1 receptor inhibitor. Simply a tolerance study at this point but looking for early clues and there’s lots of reasons to think we might know who those patients are. Our group is presenting another one, same combination, different company’s drugs and M D Anderson and the NCI did yet another study, same targets.
And of course you’re getting Baselga into the bargain in Boston.
We are. I apologise to the country of Spain because we’re importing him back again but we’re excited to work together, he and I.
What else are you doing at home, Harvard?
We’re still testing the Hsp90 pathway; we’ve got all sorts of new and intriguing new kinase inhibitors coming down the pipe. And fundamentally what we’re doing is profiling our cancers – we’re very interested in terms of saying all lung cancers are not alike, even all GISTs are not alike. You take a micro-disease like GIST and we know it’s already fifty different diseases. So now our ovarian cancer group, our lung cancer group, our breast cancer group are doing something very, very similar.
And the sarcomas?
And the sarcomas are clearly a hundred or so different diseases.
And where is that all going?
That’s going into smaller and smaller patient groups.
How many active drugs are in there, do you think?
At this point in our clinical trials we’re running at least thirty clinical trials for different smaller and smaller groups of patients, even besides GIST. Diseases like pigmented villonodular tenosynovitis, things that nobody can pronounce. But it’s very important because before if you had a sarcoma it was a sarcoma, it didn’t matter. And then you’d have something called hemangiopericytoma, which sounds like a blood vessel tumour, maybe it’s a malignancy, and actually now it’s called solitary fibrous tumour. But this is a disease that has shown spectacular responses to the combination we talked about before – the IGF1 receptor and the mTOR inhibitor. And we’re still hoping that the IGF1 receptor antagonist will work better than they’ve shown so far in Ewing’s sarcomas. There will be two presentations now showing that the data when you don’t select the right Ewing’s patients is not very good. There are certain patients who get extraordinary results but for the population as a whole is probably not good.
So that’s Gefitinib all over again?
It’s a lot of that, although with Gefitinib at least we finally figured out what the mutation was. This does not seem to be mutationally driven with the Ewing’s sarcomas, so what is it? Is it epigenetic? It’s the next level of technology so that we can tease apart the different patient groups. In some ways it’s the Ipilimumab, nobody can pronounce that drug, it’s the melanoma drug that prolongs survival.
The non anti-melanoma antibody.
The one that’s anti T-cell suppressing.
What we all want to know is what are the biomarkers for the people who are going to get the real activity and can we segregate or separate the activity from the immune toxicities. I think that’s a very important finding, obviously, and now it’s up to us to apply it to other cancers. It will probably have relevance in sarcomas; it will certainly have relevance in other carcinomas, we’re all hoping.
George, thank you very much indeed.