ASCO 2015

Nivolumab extends survival for patients with the most common lung cancer

Dr Luis Paz-Ares - Hospital Universitario 12 de Octubre, Madrid, Spain

How did you, or why did you, come up with the idea of using PD1 in a phase III study? There are studies that have gone before in lung cancer, haven’t there?

Yes. There are a number of early clinical studies with different anti-PD1 or PDL1 agents. Results on the different subtypes of non-small cell lung cancer, squamous and non-squamous, were clearly promising and this is the reason, actually, a number of investigators initiated phase III studies with nivolumab but also with some other anti-PD1s in this context.

What did you do in the study, in fact?

In this study we actually decided to compare nivolumab as compared to the standard of care, docetaxel, in patients with non-squamous histology lung cancer that had progressed to what is the standard of care in the first line, platinum based chemotherapy. So those patients were randomised and we see how good was the treatment as compared to the other in terms of efficacy but also in safety.

What in fact did you find?

We did find that the trial met its primary endpoint. There was some improvement in survival for patients treated with nivolumab, the hazard ratio being 0.73, that means a decrease in the risk of death of about 27% which translates into an improvement in median overall survival of nearly three months.

Now this was for a considerable group of patients, more than 500 patients so it was a big study. What do you conclude from that in terms of the application of this potential new therapy?

I think this trial showed that it’s clearly an effective therapy, possibly more effective and less toxic than the standard of care, docetaxel, in the particular setting of second line non-small cell lung cancer. I would say that if agencies are approving that, that I think it will, it’s very likely that this will become if not the, at least one, standard of care.

Why do you think PD1 targeting works so well rather than a cytotoxic?

The choice that lung cancers… the first thing is that we are now understanding a lot better why the immune system is sometimes not good enough to attack tumours. The reason is because we are understanding how the tumour and the host immune system are talking one to each other and they have greater interference, they inhibit the action of the other. What it’s actually doing, this drug, is actually inhibiting the escape mechanism of the tumour not to be attacked by the immune system.

Could you, in fact, use another cytotoxic chemotherapy agent plus the PD1 target together?

Yes, the truth is that we are actually evaluating that in many trials. At the present time this could be an efficacious way, on the other hand there is some risk that they are actually antagonistic because the cytotoxic therapy may attack as well the immune system cells. So, to be honest, we are not sure at the present time. There are some preliminary data that do not look bad but some more studies, particularly phase III studies, are actually needed and they are already ongoing.

But there are very different toxicities, aren’t there?

No doubt. Toxicities are totally different. As a general rule I would say, particularly for PD1 agents, docetaxel chemotherapy is a lot more toxic in terms of incidence of adverse events and severity of adverse events. Nivolumab is a pretty well tolerated drug.

So what’s your potential advice to cancer doctors moving forwards on this for non-small cell lung cancer and particularly non-squamous cell non-small cell?

I think immunotherapy is getting to lung cancer and is getting to stay. I think lung cancer doctors, we should learn more about immunotherapy because I think we will have to use those drugs, we have to know about the potential toxicities and how to manage them. We have to learn about how to be able to combine immunotherapy with other treatments because that is going to be a part of our future armamentarium.

And the brief take home message about this and in the context of using immunotherapy is what?

Immunotherapy is coming to lung cancer and it’s coming to stay. Indeed, nivolumab had improved survival in a setting of non-small cell lung cancer where treatment options were quite limited. The associated safety profile is quite favourable.