Welcome to ecancer at the ESMO meeting in Munich, I’m Gordon McVie and I’m the founding editor of ecancer. It’s about 42 years since I started the EORTC lung cancer cooperative group and at that time nobody knew anything about ALK and we’re going to talk about nothing but ALK. ALK is anaplastic lymphoma kinase and thank goodness we’ve found this subset of non-small cell lung cancer patients because we’ve also got really good drugs for tackling them, including tackling patients who have got ALK positive disease in the brain and these are really interesting times. With me to discuss the data is Dr Martín Lázaro from Vigo in the top left hand corner of Spain. Martín, thank you very much for joining us.

Thank you.

Tell me about how your practice in treating lung cancer patients changed after the ASCO meeting this year.

We treated the ALK positive lung cancer patients with crizotinib but now we treat ALK positive lung cancer patients with alectinib from the data of the ALEX trial. The ALEX trial demonstrated that alectinib is superior to crizotinib and, more important, alectinib has a protective effect against brain metastasis.

What size of impact was that in the trial that was reported at ASCO?

Alectinib delayed the onset of brain metastasis and this is a highly important issue for lung cancer patients because brain metastases have an impact on quality of life.

So here we are at ESMO and there has been more data about the comparison and there’s also third generation drugs coming up now, more tyrosine kinase inhibitors which are targeted on ALK and also on ROS. So tell me about the data presented in ESMO in Munich now.

In Munich alectinib has a trial, the ALESIA trial, that demonstrated the superiority of alectinib versus crizotinib in first line treatment of lung cancer patients ALK positive but in an Asiatic population. This confirms the data with the ALEX trial but in this subset. The data are impressive because the primary endpoint was progression free survival and the hazard ratio was about 0.2.

And the progression free survival for each was what?

The progression free survival was not reached in the alectinib arm and about 11-12 months in crizotinib.

So that’s impressive. Any brain metastasis data come out yet or is it too early?

It’s too early to know the data.

What about the toxicity in both arms of these trials?

As in the ALEX trial the toxicity favours the alectinib arm with a better profile of toxicity than crizotinib.

What do you get in terms of side effects from alectinib?

The patients have less probability of severe toxicities with alectinib and that we can manage.

Are the side effects bone marrow or are they…?

No, diarrhoea and elevation of transaminases are perhaps the most important.

So it’s important to know that if you see an elevation of transaminases it’s not necessarily the cancer, it could be the drug.

It could be the drug.

Because that’s important, otherwise you might stop the drug.

Yes, and perhaps to lower the dose, administer a lower dose in the case of toxicity.

So tell me about the other drugs that are in ESMO here because there are other ones now, aren’t there? There are two or three that I’ve seen.

In ESMO there are data of lorlatinib about quality of life in patients, patient reported outcomes, the PROs. Lorlatinib has a favourable impact on quality of life of patients. There are data of ceritinib after chemotherapy in second or third line with progression free survival that is 50 months. Also there are data of brigatinib in third line, Sanjay Popat reported data about the activity in brain metastases with a response rate of 83%.

Eighty? Eight zero? This is impressive, no?

It’s impressive because with crizotinib the response rate is about 50%. And we have also data about ALK variants with alectinib that confirms that alectinib is superior to crizotinib regardless of ALK variant.

So the ESMO have changed the guidelines since the ASCO meeting, what do the ESMO guidelines say now, today?

Today ESMO guidelines put alectinib as the first choice to treat ALK positive lung cancer patients. The last guidelines were two years ago and we have only crizotinib in this context.

So we’re moving forward?

Yes.

So in your practice now when you go back to Vigo you can get alectinib?

Yes, it’s in use.

It’s through the EMA?

We use alectinib in the first line setting due to the activity of alectinib versus crizotinib.

And which drug do you use in the failure of alectinib?

We have less data about the sequence but perhaps the third generation inhibitors maybe the option to use in this context.

And they’re all on trial, they’re not yet through the EMA.

On trial, yes.

So the conclusion is that it looks as if crizotinib is now in second place, is that right?

Yes.

And then beyond the failure of crizotinib and alectinib there are still at least three other drugs which are active and which actually affect brain metastases?

Yes, this is a very important issue within second and third generation drugs.

So the new patient with brain metastases first line, what do you do?

If he is asymptomatic we treat with alectinib and only use radiotherapy or radiosurgery in case of symptomatic patients with target lesions treatable with radiosurgery. We try to delay the use of radiotherapy due to secondary effects, secondary alterations in cognitive function.

Thank you very much indeed, Martín.

Thank you.

That’s a brief but impressive overview of the development of the best management for patients who have got non-small cell lung cancer who are ALK positive. I have to say again and again that all patients with non-small cell lung cancer should be tested, not just for ALK but for a range of new tumour markers which will help us choose the best treatment. But for ALK there’s been a field change, no question about that. We were excited about crizotinib several years ago and now we’re moving on to the second generation and alectinib seems to be the front runner at the moment but there are third generation tyrosine kinase inhibitors coming along the line. Patients who present with brain metastases are still possibly going to be responsive to these new tyrosine kinase inhibitors which is really great news and patients who develop brain metastases on chemotherapy or on crizotinib or on alectinib, they can still be rescued and this is seriously good news. So we’re pushing the boundaries from my time forty years ago which was something like seven or eight or nine months, we’re into the two year, three year mark and that’s really quite impressive progress.

Thank you very much indeed again, Martín, and thank you for watching ecancer.