Medicine Matters oncology

And here we are as ESMO 2019, Barcelona. Back to Barcelona, because we were here at World Conference on Lung Cancer only a couple of weeks ago.

And what is there in the thoracic oncology space? Well, I guess in the presidential plenary session, we saw overall survival from FLAURA. So in the United States, FLAURA established osimertinib, a third generation EGFR inhibitor, as the de facto first line treatment since it had a longer PFS than first generation EGFR TKIs.

But in some countries, because sequential therapy could still be done, start on the first generation drug, wait till you progress, if you have to have T790M, then go on osimertinib. I think showing an overall survival advantage of about six months difference in median overall survival is going to be enough to carry it over the threshold in some countries.

There was an update on CheckMate 227, which is, generally speaking, a pretty complex trial. It was an ipi-nivo arm, a nivo, and a platinum doublet arm. And we've seen the data presented in a number of different ways, sliced in a number of different ways. So I think there's an element of kind of observer fatigue associated with it.

I think it's really hard to know whether ipi-nivo is really going to have a place in non-small-cell lung cancer. It does show a somewhat higher response rate, longer duration of response. But I don't know that nivo is a drug that we think has got a future, given that pembrolizumab in multiple studies seems to be looking better.

So if CTLA4 antagonists do have a role in non-small-cell lung cancer, I don't know if it's going to be in combination with nivolumab. I don't know if the degree of benefit and their additional toxicity are really justified. I think it's going to be a challenge for BMS to convince to use that doublet.

We saw in the ALK field a couple of small updates. Yet another study showing that brigatinib post-next generation inhibitors is getting response rates of about 50% and median progression free survivals between five and six months. So looking almost identical to lorlatinib in that setting, potentially better tolerated. So that's certainly one to watch.

For lorlatinib, we saw the formal presentation of both intracranial and extracranial response rates. So not just overall response rate, but extracranial. And that's nice, because I think that's the way data should be shown in the future.

And from that, we can see that every time they assessed it, in every one of their cohorts, the response rate was higher in the brain than it was in the rest of the body. And I think that's partly because when people have come off other drugs, because none of them have got perhaps as good a CNS penetration as lorlatinib. The brain is behaving as if it's in an earlier line of therapy, as if it's more treatment naive. And certainly, that's one of the real strengths of lorlatinib, but also perhaps explaining some of its side effects, its cognitive side effects present in about 54% of people.