TRK Inhibitors: A Tumor Agnostic Targeted Therapy - Episode 5

Understanding Larotrectinib's Safety Profile

Shubham Pant, MD:Tell me about safety. How did the patients do on the trials? What kind of safety signals were there? What kind of adverse events can we look for in these patients?

David S. Hong, MD:So in the larotrectinib trials, the drug was incredibly safe. And I can say that personally because I’ve treated many of these patients and the most common adverse effect is fatigue, mostly grade 1 or 2 adverse events, which was really minimal, and oftentimes we did not do anything to alter their course in that sense. The second-most-common adverse events included a slight dizziness, which was not unexpected given the fact of targeting this molecule. And at least with larotrectinib there was an increase in the AST too.

Shubham Pant, MD:I think liver enzymes were elevated.

David S. Hong, MD:Liver enzymes, yes, I’m sorry. Larotrectinib has a slightly different safety profile. In the most recent data that were presented at ESMO [the European Society for Medical Oncology Congress] with around 55 patients, the most common adverse effect was actually dysgeusia, which is this taste change. And constipation and diarrhea were also very common adverse effects with entrectinib. And that may just reflect the multikinase nature of entrectinib versus larotrectinib.

Shubham Pant, MD:OK, so tell me this. Were there any patients who were taken off for serious adverse effects or something? Are there any serious adverse effects that you see a little bit of in this? You see dizziness; you see all these adverse effects that one should watch out for. Are there any serious adverse effects for which patients came off it?

David S. Hong, MD:Offhand in both the phase I and phase II, I don’t think there were any patients who were immediately taken off for secondary to severe adverse effects. Some of them eventually did come off for progression of disease. Some of those patients did have grade 3 events, but again, the rate was very low, lower to other drugs that we tested in the early setting. And so, again, the overall safety profiles of both larotrectinib and entrectinib have been really favorable.

Transcript edited for clarity.