European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2013

New targets for squamous cell carcinoma

Dr Martin Reck – Hospital Grosshansdorf, Wohrendamm, Germany
 

Martin, everybody is knowledgeable about the fact that with adenocarcinoma you have a lot of targets but squamous cell carcinoma of the lung is a difficult one, isn’t it? But you’re actually rather optimistic about it at the moment, to some extent, because you’ve got some new targets. Tell me what you’ve been working on, please.

The squamous also has entered the stage quite slowly but now we have identified new targets for really personalised inhibition of certain patients with advanced squamous cell cancer. In particular we have three areas that we are looking for: one is the PI3K pathway where we do see certain alterations; now we have specific agents inhibiting the PI3K kinase pathway. The other one is FGF so we do see that in a substantial group of patients with squamous cell lung cancer there is an amplification of FGF and this is crucial for tumour cell proliferation. Now we have the first agents in place to look on the inhibition of the FGF mediator, FGF mediated pathway. The third one, this is a quite rare alteration but it’s also substantial, this is the DDR2 mutation where we also do see certain effects on certain drugs.

So in your clinical work you’re actually doing some studies, aren’t you, on some of these targets?

Yes.

What have you been able to do so far?

Now we are in the very early stages so we look for the safety of the drugs; we look for the appropriate dosage of the drugs but now we are moving forward, we extend the groups of patients that we are treating and we are looking forward to develop randomised protocols to have a very key proof of the efficacy of these drugs.

So there are targets and there are pathways that you can influence with practical agents that could be valuable?

Yes, even in squamous cell there are certain pathways that we may inhibit by certain drugs.

How far has this got so far with squamous cell?

This is the first step; we are still far away from the phase III trials. This is something I would expect for the next years. The other concept, and this is something we are also entering in squamous cell, is the concept of immunotherapy. This is quite exciting; we do know that there is a field of immune suppression around the cancer and now we have identified certain structures to overcome with certain agents.

What are those structures that you’ve identified, then, that are responsible for suppressing immunity around the tumour?

Coming from a therapeutic point of view, currently we are talking about two, we call them, checkpoints. One is the CDLA-4 receptor, which is important for the early T-cell activation after contact with the antigen presenting cells, and the other is the PD-1 receptor and the PDL-1 ligand. There we do have specific antibodies to inhibit the structures and to restore the immune capacity of the tumour.

Where does ipilimumab come in then?

The first data we have seen in melanoma, and there we have seen tremendous results, this has been the first drug to show an improvement in overall survival in this disease. We have performed a randomised phase II trial of the combination with ipilimumab and chemotherapy in patients with advanced lung cancer. What we did see was an improvement of progression free survival, this was the primary endpoint, and very surprisingly the largest benefit was seen in patients with squamous cell carcinoma. Now we are running into a large phase III trial investigating the efficacy of ipilimumab in patients with advanced squamous cell lung cancer.

What should busy cancer doctors make of these developments? They sound very promising but, as you say, that phase I/phase II level at the moment. But you are working in patients and they are looking promising.

Yes. I think it would be very keen to have more patients on clinical trials. I just would give a strong argument to be aware of the clinical trials which are out now and to look for cancer centres who are participating in these clinical trials because we only will get well knowledged about the efficacy of the drug if we really are able to run these trials in patients with advanced cancers.

OK, so you’ve got the immunotherapy, you’ve also got the new targets, the squamous cell carcinoma, can you give me some kind of idea about how much scope there is that these could really impact patient outcomes in non-small cell lung cancer?

I’ll tell you a very simple story. Data were released last year at ASCO and this was about inhibition of PD-1 by a specific antibody. The response that we have seen in heavily pre-treated patients was 25%. Currently, with second line treatment, in advanced non-small cell lung cancer we do expect a response in the range of 7-8% by conventional chemotherapy. So this is substantial progress and we really do expect a lot of efficacy of these new treatments. So we do not have the survivor data, we will need the clinical trials to explore the efficacy of these drugs but there is a lot of expectation on these new pathways and these new therapies.

So in a few words, do you think doctors should look forward to a situation where squamous cell carcinoma of the lung is not such a daunting prospect for treatment?

Yes, I definitely would support this belief.

And what do the doctors need to do to make that all happen?

What we need is the analysis of the tissue; we need to screen for the molecular alterations and, as I mentioned before, they really should look out for cancer centres who are participating in clinical trials because this will be crucial for the improvement of care for patients with advanced squamous cell cancer.

So the biomarkers are the key at the moment?

Yes.

Martin, thanks very much for joining us here on ecancer.tv.