TRK Inhibitors in Lung and GI Cancers - Episode 12

Approaching Treatment for TRK Fusion–Positive Cancers

, , , , ,

John L. Marshall, MD: Jyoti, I couldn’t believe it when it happened, but there’s a second drug approved, entrectinib, and it’s basically the same space. Maybe you could give us that big picture about if it is a different mechanism, or why would you decide one versus the other?

Jyoti D. Patel, MD:Sure. Larotrectinib is so well tolerated that we see patients getting back to function, and we’ve seen long duration of responses. When entrectinib was approved, it added another option for our patients. Entrectinib is a little bit different in that it has activity against a number of kinases. We know that there is also ROS1 and ALK activity, and so it’s been actually approved for both kinases.

For entrectinib, the earlier trials were based on a number of basket trials as well as a pediatric study, and the number of patients with CNS [central nervous system] metastases was a little bit higher. Perhaps there are more data there, particularly for those of us that deal with lung cancer, in which we see patients with ROS1 disease and translocations who have a proclivity for brain metastases. That figures into our rubric of putting these drugs together.

I would say that the clinical activity profile, to me, is functionally pretty similar. The total number of patients that we see who have been treated across these trials is very small and limited. Suffice to say, there are more patients with CNS metastases treated with entrectinib, so perhaps a little greater experience there.

The toxicity might be a little bit of a different story, a little bit more fatigue with entrectinib, and some weight gain, at least in my experience. Patients have had a little bit harder time with some of these low-grade toxicities. But again, for someone with known CNS metastases, that may be a way to tease these out. But again, these are small-number studies looking at different pockets of patients, 1 larger basket as opposed to subgroup analysis of some smaller ones.

John L. Marshall, MD:Yeah, that’s very insightful. Shubham, have you used this drug at all, entrectinib, and is it equally active across all of the 3 subtypes?

Shubham Pant, MD:Yes. So I think it does the same thing, just as Jyoti said, so it does the NTRK1, NTRK2, and NTRK3 in all 3 genes, essentially ALK and ROS1 for rearrangements. I think it’s fairly similar. Most of my experience has been more with larotrectinib than entrectinib, but I think…the data seem to be fairly similar. Just as Jyoti pointed out, brain metastases and everything, they looked at that, so we have larotrectinib data with brain metastases also.

John L. Marshall, MD:Yeah, that’s great.

Transcript edited for clarity.