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ONCAlert | Upfront Therapy for mRCC

Further TRK Inhibitor Development

Targeted Oncology
Published Online:1:24 PM, Wed February 20, 2019

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.

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.
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