Novel “Tissue-Agnostic” Targeted Treatment - Episode 4

Advocating for Early NGS Testing to Identify TRK Fusion


Alexander Drilon, MD: My preference in terms of doing a comprehensive test like NGS [next-generation sequencing] is to do that whenever you can. So obviously it’s most reasonable to do NGS when you have a patient with stage IV disease, and it helps you pick the frontline therapy that’s best suited for a patient. Meaning, if they have a certain driver I would obviously sequence them to target therapy up front. But I think you can make a very strong case for doing NGS, even on early stage cancers. Because even if a targeted therapeutic is not specifically approved in stage I to III cancers, you still have knowledge that that cancer harbors a particular gene signature and keep that in your back pocket so that if patients do develop recurrent disease, you can very quickly sequence them on the best possible therapy.

Now, going specifically to TRK fusion—positive cancers, I think this is slightly different from some early stage lung cancers where there’s no approved targeted therapeutic for stage I to III. Because in the regulatory dataset for larotrectinib, there were certainly patients [who] had advanced bulky disease that was nonmetastatic. And an example of this would be there were some kids that had congenital fibrosarcomas that harbored a TRK fusion, really bulky tumors of the knee. These would unfortunately have required leg amputations for therapy. But we very early on recognized the presence of a TRK fusion in these cancers, got them on to larotrectinib, [and] had really dramatic responses to therapy where the tumor really appreciably shrank down.

And we got these kids to limb-sparing surgery. And lo and behold, when the pathologist looked at what they thought was possibly residual tumor, there was no cancer in the specimen, meaning they had what we call a complete pathologic response. And so, this really highlights the utility of doing neoadjuvant therapy for certain earlier stage cancers, and that [is] improving outcomes and hopefully improving cure. And it makes a pitch for looking for these fusions early on whenever you can. As long as there no barriers to payer insurance coverage for next-generation sequencing testing, I personally would advocate trying to do that as early as possible.

Transcript Edited for Clarity