TRK Inhibitors: A Tumor Agnostic Targeted Therapy - Episode 6

Drawing Larotrectinib Data From Different Tumor Types

January 28, 2019

Shubham Pant, MD:Dr Hong, tell me about what kind of tumors there were in the clinical trials.

David S. Hong, MD:So of the initial 55 patients in the larotrectinib data set that we shared, probably if you looked at all the different subsets and categories, the largest category was really sarcomas: gist, undifferentiated sarcoma, etc. And then the other categories were probably MASC [mammary analogue secretory carcinoma] tumors, which are these tumors that arise from the head and neck, oftentimes mistaken for salivary gland or parotid tumors.

Shubham Pant, MD:So they’re not salivary gland tumors; they’re different from that.

David S. Hong, MD:I think they’re a subset of salivary gland tumors.

Shubham Pant, MD:Got it.

David S. Hong, MD:And they’re oftentimes mistaken for just standard salivary gland tumors. And so if you have an expert pathologist look at them, oftentimes there can be clear differences. And then, some of the pediatric tumors were included in that initial 55 data set. And then when we updated the most recent data set of 122 patients at ESMO [the European Society for Medical Oncology Congress], in some patients who were enrolled, there was additional subsets of tumor types like thyroid cancers that we identified.

So as I shared, I think we don’t fully know the full prevalence across all different histologies. However, we do think that they do exist in most histologies. And I think we will find out—now that Vitrakvi is approved, and as people are looking for these patients in their NGS [next-generation sequencing] panels or their regular practice—that that number may be further defined as more and more patients are enrolled in these trials or get this drug.

Shubham Pant, MD:So what you’re saying is for salivary gland tumors, a subset is very highly expressed, and most of them would benefit if they came to practice and you used NGS. And it’s a bigger and broader discussion for later, but those cancers seem to have a high percentage, especially in this subset of salivary gland tumors.

David S. Hong, MD:Correct. And I think what’s also interesting is that beyond the pediatric subset of patients, the vast majority of patients that we identified were younger. So for example, a patient with lung cancer who was a nonsmoker, who did not haveALK, ROS, EGFRalterations, was identified as having this. Another example would be that many of these patients who have papillary thyroid cancers likewise tend to be younger and have more aggressive disease—patients who do not have any of the classical alterations that we see with papillary thyroid, whether it’sRETorBRAF, etc. These are keys and clues to trying to see and identify these patients who may need further NGS screening with a fusion assay of some sort in order to help identify these patients.

Transcript edited for clarity.