Looking Ahead in the Treatment of NSCLC


Paul K. Paik, MD, considers the future of MET-directed therapies in non-small cell lung cancer.

Briana Contreras: What do you see happening in the future in terms of MET-directed therapies for non–small cell lung cancer?

Paul K. Paik, MD: We’re at the beginning of trying to figure out the best treatment options for patients with MET exon 14 skipping, so the future will rely on a couple of things that are in active clinical development. The first thing to consider is a whole other way of targeting MET, which we’ve tried before, and that has to do with antibody-directed therapies. This would either be pure antibodies against MET or antibody-drug conjugates. This is a very interesting way to target MET, which is in active clinical development or early phase trials. That’s 1 future direction—your term—that holds some promise.

Whether we prescribe that by itself or in combination with MET tyrosine kinase inhibitors [TKIs] like tepotinib or capmatinib—we’ll have to end up seeing what happens. The other element has to do with why patients develop resistance to MET-directed therapies like tepotinib and capmatinib. We’re trying to figure this out with the idea that we can then circumvent those resistance mechanisms with another drug, ideally another targeted therapy. That’s something that’s on the horizon that, hopefully, we’ll be able to crack relatively soon.

Briana Contreras: Lastly, I have another question for what you predict in the future. What do you expect to see in the next 5 years in targeted therapy in general for non–small cell lung cancer?

Paul K. Paik, MD: Oh, that’s a hard question to answer. In the next 5 years, there are going to be a couple of things that we see emerging. The first is that we may end up finding some newer targets. But at this point, with all the sequencing work that we’ve done, it’s unlikely that we’ll find a traditional target. That’s a target that occurs in the DNA, that happens with an appreciably high frequency. We’ve mined these data sets quite a bit and really haven’t uncovered anything. I do think that targeted therapy development, in the next 5 years, will begin to shift away from DNA to a different understanding of how these alterations affect cancer biology, and whether that has to do with how these alterations affect responses to immunotherapy, for example, or metabolism, which we might be able to target. That’s the next step in targeted therapy development that we’ll begin to see in the next 5 years. In the next 5 years, we’ll also begin to delve into other biological processes, so the kinds of targeted therapies we develop will end up being different from what we’re used to. Instead of these inhibitors of specific pathways, we may see inhibitors of the immune microenvironment, metabolism, or metastases formation. Basically, there will be an evolution of how we’ve been targeting things that help us figure out what the next big step is going to be in trying to identify new treatments for our patients.

Briana Contreras: Thank you so much for your time, Dr Paik. I hope that everybody found the information to be valuable to your clinical practice. Thank you all for watching this Managed Healthcare Executive® program from MJH Life Sciences.

Transcript edited for clarity.

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