ELCC 2018 | The need for RCTs in immunotherapy for mesothelioma

Dean Fennell

Speaking from the 2018 European Lung Cancer Congress (ELCC) in Geneva, Switzerland, Dean Fennell, PhD, FRCP, of the University of Leicester, Leicester, UK, stresses the need for increased randomized controlled trials (RCTs) looking at immunotherapies for treating mesothelioma, to establish its efficacy for cost-benefit analysis. Prof. Fennell also talks about the potential of gene knockout, particularly of the BAP1 gene.

Transcript (edited for clarity):

I think the angiogenesis will have a lot of promise, and again if we can see the effects of nintedanib within a mesothelioma as we’ve seen in the LUME: Meso study, and I think we have a new option for therapy. that’s my hope.
I think in terms of the second line setting, immunotherapy is an extremely a big opportunity here to be had. It will take randomized trials, I think, for the regulatory authorities to be able to justify the high costs of these classes of agent, but the signals are there. Indeed we have had a global randomized phase 3 trial already recruit, which is the checkmate 743 study.
In terms of genetics, mesothelioma is unusual; there are not a lot of mutations, that are evident as potential targets. BAP1 is one, NF2 is another. Beyond that, there are very few point mutations that could be considered as drivers that could be actionable therapeutically.
The disease is one in which a lot of the genes have been knocked out; so-called tumor suppressor losses, and this has been a big challenge in therapeutics generally, how do you target these? But I’ve already mentioned BAP1 as a new opportunity, that is a tumor suppressor and if we look to others CDKN2A may be a new option, particularly with what we’ve discovered recently with PRMT5 as being a possible synthetic lethal partner.

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