TRK Inhibitors: A Tumor Agnostic Targeted Therapy - Episode 8

Further TRK Inhibitor Development

Shubham Pant, MD:Tell me, there are other TRK inhibitors out there. So we talked a little bit about entrectinib you said it got like a breakthrough designation. How does that target the TRK? How is it different from other TRK inhibitors?

David S. Hong, MD:So entrectinib is different than larotrectinib in the sense that it also targets ALK, ROS. And the most recent data that came out were also at ESMO [European Society for Medical Oncology 2018 Congress]. Dr George D. Demetri, MD, presented those data. He’s from Dana-Farber Cancer Institute. And in that dataset there was I think about 55 patients. The response rates were slightly lower than larotrectinib, about 57%. As I shared with you, the actual adverse event profile was a little bit more different. The most common adverse effect being dysgeusia.

Shubham Pant, MD:And that was with entrectinib.

David S. Hong, MD:Yes.

Shubham Pant, MD:So as you said entrectinib followed larotrectinib, you said it’s more for like dizziness or…

David S. Hong, MD:Yes. Fatigue.

Shubham Pant, MD:Fatigue was the big one, yes.

David S. Hong, MD:So what’s also interesting is that in the entrectinib dataset they did reach a median, it’s called duration of response, of around 10 months, which at this point with larotrectinib—the dataset that we have of the 55 patients, the initial dataset—we have not even reached a median duration of response. Over 80% of the patients with larotrectinib do appear to at 1 year still maintain their response.

Shubham Pant, MD:All these seem to be durable responses. That means it’s not like one of those drugs that the response happens and then it goes away.

David S. Hong, MD:Correct. And whether that’s entirely because of larotrectinib or just the biology…

Shubham Pant, MD:The biology of the disease, like in slower growing salivary gland tumors.

David S. Hong, MD:It’s not entirely clear yet. And the numbers are too small I think right now for both the entrectinib and larotrectinib for us to make any clear comparisons. I know there are a lot of people who would like to make comparisons between those.

Shubham Pant, MD:But these are different trials, so you cannot cross-compare trials.

David S. Hong, MD:At this point, yes.

Transcript edited for clarity.