TRK Inhibitors: A Tumor Agnostic Targeted Therapy - Episode 9

Tumor Agnostic Treatments: A Changing Paradigm

Shubham Pant, MD:Dr Hong, tell me, with these new TRK inhibitors, this is one of the first tumor agnostic approaches. That means it doesn’t matter what tumor you have, it’s the fusion you can get. You can get the same therapy. And with microsatellite unstable patients, it doesn’t matter what sort of tumor you have, if you’re microsatellite unstable you can get immunotherapy. Tell me, how do you look at this paradigm shift in the way we treat solid tumors? Do you think this is one off, or do you think this is the start of a new era in solid tumor oncology?

David S. Hong, MD:That’s a really good question. I think that if anything, there’s a paradigm shift in how the FDA has looked at the regulatory package and the regulatory pathway for some of these new agents. And I think they’ve been very much more open to the fact that as in, for example, pembrolizumab or nivolumab with MSI [microsatellite instability]-high tumors, we’re seeing activity and benefit across histologies independent of what histology it is based upon this molecular marker, which is MSI high. Larotrectinib or Vitrakvi’s approval just recently is really the second tumor agnostic indication that has been approved. Do I think this is a one-off? No, I think there will be other drugs in the near future that will also target pan tumor, whether it’s fusion, whether it may be even TMB, which is tumor mutational burden with immunotherapy. I think there will be other drugs that emerge. I think that the vast majority of cancer treatment will be based upon histology.

Shubham Pant, MD:And this is in breast cancer, lung cancer, colon cancer?

David S. Hong, MD:Correct. But I think there will be increasingly more of these drugs that will truly be tumor agnostic, that if you have X mutation or if you have X fusions, the therapy will be driven by that more so than the actual histology of the cancer.

And I think that really comes from the fact that we see 2 trends. One is that we are understanding the tumor on a much more molecular level and that it’s kind of infiltrating into community, right? Next-generation sequencing is becoming much more prevalent. A much more detailed analysis will emerge. In addition, there will be more and more new drugs that can target some of these alterations across tumor types.

Transcript edited for clarity.