ELCC 2018 | Therapeutic targets for mesothelioma and sarcomatoid carcinoma

Dean Fennell

In this video, Dean Fennell, PhD, FRCP, of the University of Leicester, Leicester, UK, discusses upcoming therapeutic targets for mesothelioma and sarcomatoid carcinoma. Speaking at the 2018 European Lung Cancer Congress (ELCC) in Geneva, Switzerland, Prof. Fennell talks about the drugs bevacizumab and nintedanib for targeting angiogenesis, immunotherapeutic treatments including nivolumab, pembrolizumab and ipilimumab, and also potential targets for genetic therapy such as the ASS1 protein and the BAP1 gene.

Transcript (edited for clarity):

At the moment things are really quite exciting, we actually have a number of targets and these have been concurrently developed so we’re beginning to see new, promising opportunities across a number of fronts. I’ll start first of all with angiogenesis, because this is where we’ve already seen evidence of activity a drug known as bevacizumab, showed a positive signal of activity, this was a couple of years ago from the French IFCT group, where using bevacizumab, they were able to improve upon the standard of chemotherapy, this was published in The Lancet.
Since then we’ve seen data from another agent known as nintedanib, which in a randomized double-blind placebo-controlled trial, showed a superiority for combination of nintedanib with chemotherapy, and this led to a Phase III trial which has recently been completed, we’re waiting the results of. I think the other key areas at the moment would be immunotherapy, as with other areas of cancer, immunotherapy has a lot of promise, certainly for mesothelioma, biggest challenge at the moment is really who to target, so which patients would be the best to target with this type of therapy, as not everybody benefits.
But where we stand at the moment with immunotherapy is that we are seeing interesting activity, we’re seeing it with single agents such as pembrolizumab, on nivolumab, and again from the IFCT, this is the French cooperative group, we’ve seen evidence now in the MAPS-2 trial of combination nivolumab and epilumimab showing very interesting effects in terms of survival.
I think beyond that, we’re still at the very beginning when we think about molecular or genetically targeted therapies. I think there are two at the moment which would be the front runners for me in terms of the the possibility of seeing outcomes of the favorable, the first is to do with a protein called a ASS1, which is an epigenetic biomarker, this is a protein which can be now targeted and a study known as ATOMIC is evaluating that in the sarcomatoid and biphasic patients as a first-line therapy.
The second i think, is the gene BAP1, and this is the most common in mesothelioma, and BAP1 has been found to be sensitizing to a new class of drug call the EZH2 inhibitor, we’ve just completed now a global study with the French, UK and the US, looking at an EZH2 inhibitor called a tazemetostat, and tazemetostat appears to be at least in the laboratory, a drug which can control cancers at the BAP1 mutated, not those that aren’t, but those that are, and the study was to test the hypothesis that in BAP1-negative tumors, they would respond. Now the trial has accrued and we just again waiting to see the results of that hopefully later this year.

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