Nintedanib in combination with standard second line therapy in lung cancer

Bookmark and Share
Published: 3 Jun 2013
Views: 6423
Dr Martin Reck - Hospital Grosshansdorf, Wohrendamm, Germany

Dr Martin Reck talks to ecancer at the 2013 ASCO Annual Meeting about a large scale clinical trial investigating combination therapy of nintedanib with standard second line therapy.

Nintedanib is anti-angiogenic drug and targets EGF and ALK; however, Dr Reck discusses the potential problems with this drug and a lack of predictive biomarker.


ASCO 2013

Nintedanib in combination with standard second line therapy in lung cancer

Dr Martin Reck - Hospital Grosshansdorf, Wohrendamm, Germany

Martin, you’re presenting a study here on nintedanib. Now there are a whole lot of new targeted therapies and in this case lung cancer. I know there are a lot of very fascinating developments in lung cancer that some people are building up to the idea that we might really make huge progress against it in the future. It sounds a little over the top to me, what’s your feeling about this?

That’s totally correct but we have to differentiate the treatments a little bit. We have the targeted therapies and oncogenic altered populations like the EGF receptor mutant or the ALK mutant; there we do see very amazing responses with dedicated treatments. The drug that I have investigated, nintedanib, this is an anti-angiogenic drug, this VEGF TKI. The problem that we have, up to now we do not have a very good predictive marker so the expectations might be a little bit lower compared to the other targeted therapies.

Tell me about this study, then, that you’re presenting here at ASCO.

This is a very large study, it’s a 1,300 people trial and we investigated the combination of this drug, nintedanib, this is an oral drug, in combination with second line treatment, this is docetaxel, compared to docetaxel in pre-treated patients with advanced lung cancer. The particular information about this is the fact that we included all histologies because conventionally all these anti-VEGF agents did show very high toxicities in patients with squamous cell lung cancer but we did include all of them.

So why are you using this particular anti-angiogenic because there are others that are already in use?

This is correct and we have seen a high number of negative trials investigating several anti-angiogenic agents in this setting of treatment. The interesting part of this drug is that this is, number one, a highly selective drug on anti-angiogenic pathways and, on the other one, it’s covering several mechanisms of anti-angiogenesis. So it’s inhibiting the VEGF receptor, the PDGF receptor as well as the ADF receptor. So we are looking on the endothelial cells but we are also looking on the stromal cells, on the interaction with the vessel related stroma. This is very unique about this compound.

This is a randomised double-blind phase III study. How promising is it looking so far?

The data are really exciting and the results are going to be very promising. We are looking at progression free survival but we are also looking at overall survival and I think the data will be very important.

What’s the downside of using nintedanib?

Up to now the setting now that we were exploring is second line treatment, so after failure of progression of first line chemotherapy then we explored nintedanib in combination with chemotherapy. We are going to see whether this will be true for all patients or for certain subgroups that were dependent on the data of the trial.

And toxicities would be what?

We have a number of toxicities that we would expect like bleeding events or hypertension or vascular related events. Up to now, as far as I can see, the tolerability was manageable.

Although you’re taking all comers in this particular study, does it look as if this is a drug for all categories of non-small cell lung cancer?

It seems so. We have to wait for the full data but at least when we performed the trial we didn’t see any unexpected safety signal in the populations. In particular we didn’t observe any unexpected safety signal in patients with squamous cell histology.

You’re looking at patients who are progressing, is there any indication that this could be extended to earlier stages of the disease?

This would be very exciting but these are future trials which we have to perform.

What are the clinical implications, then, coming out of your study?

If this is really going to work we will have a new option for second line treatment in patients. This might be very important.

How would nintedanib fit into the spectrum of therapies then, in your opinion, as of now?

I think it would be very interesting for patients without oncogenic alterations like EGF receptor mutations or ALK translocations. This could be a drug for the non-addicted populations.

So in other words, patients who haven’t got a target, you can use this?

Patients where up to now we haven’t identified a target.

Yes, yes. So how would you sum all of this up for busy cancer doctors right now?

We are expecting very exciting data and I think that this data will have an impact on practical clinical management of lung cancer.

Martin, thanks very much for joining us.