Future Directions for Precision Medicine in Advanced NSCLC - Episode 10

NTRK Gene Fusions: Rare Yet Actionable


Benjamin P. Levy, MD: So, similar to the theme of rare yet actionable mutations, let’s move on to NTRK fusions. This has been a unique story. A tissue-agnostic trial basket study looked at patients anywhere from 4 months of age all the way up to those in their mid-70s who had solid tumor malignancies that harbored specific NTRK fusions. Treatment with larotrectinib showed really incredible results—practice-changing. Lyudmila, do you want to talk about that data which [were] just recently published?

Lyudmila A. Bazhenova, MD: So, NTRK fusions are even more rare than BRAFV600E-mutant lung cancer. You can’t find NTRK fusions on regular next-generation sequencing. We have fairly impressive data on larotrectinib in that patient population. As Ben already mentioned, this was a combination of childhood cancers as well as adult cancers. There were a total of 55 patients, and response rates to larotrectinib [were] 75%. In lung cancer, we have not seen such high responses, with a couple of exceptions: of ALK patients, and, maybe, EGFR-mutant patients. What’s also important is that response appears to be quite durable. So in the presentation, the median progression-free survival has not been reached. But at 1 year, 71% of the responses were still ongoing.

To me, this is completely practice-changing. Most likely, you will not see, or may see, just 1 patient with an NTRK mutation in your lifetime. But I would say even a single patient with an NTRK mutation missed is 1 too many. The response rates are so great, and you do have an access for community oncologists. You know that your nearest academic institution most likely has an NTRK drug or you can find an NTRK drug somewhere close by.

Another thing that is important about larotrectinib is that it’s extremely well tolerated. The majority of the adverse events were grade 1. So, patients did very well. Responses were quick. I personally have not yet seen a lung cancer patient with an NTRK mutation, but I have treated both a thyroid cancer patient and a colorectal cancer patient with an NTRK mutation. Both had really good responses on clinical trial.

Benjamin P. Levy, MD: It really underscores the importance of next-generation sequencing. I think comprehensive genomic profiling is critical to identify. This is not just a story about EGFR or ALK. This is a story about other rare, actionable mutations also in the context of PD-1 [programmed cell death protein 1] testing, and we’ll talk about that.

Transcript Edited for Clarity